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1.
Occup Environ Med ; 80(8): 425-430, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37295943

RESUMO

BACKGROUND: Pneumoconiosis among coal miners in the USA has been resurgent over the past two decades, despite modern dust controls and regulatory standards. Previously published studies have suggested that respirable crystalline silica (RCS) is a contributor to this disease resurgence. However, evidence has been primarily indirect, in the form of radiographic features. METHODS: We obtained lung tissue specimens and data from the National Coal Workers' Autopsy Study. We evaluated specimens for the presence of progressive massive fibrosis (PMF) and used histopathological classifications to type these specimens into coal-type, mixed-type and silica-type PMF. Rates of each were compared by birth cohort. Logistic regression was used to assess demographic and mining characteristics associated with silica-type PMF. RESULTS: Of 322 cases found to have PMF, study pathologists characterised 138 (43%) as coal-type, 129 (40%) as mixed-type and 55 (17%) as silica-type PMF. Among earlier birth cohorts, coal-type and mixed-type PMF were more common than silica-type PMF, but their rates declined in later birth cohorts. In contrast, the rate of silica-type PMF did not decline in cases from more recent birth cohorts. More recent year of birth was significantly associated with silica-type PMF. CONCLUSIONS: Our findings demonstrate a shift in PMF types among US coal miners, from a predominance of coal- and mixed-type PMF to a more commonly encountered silica-type PMF. These results are further evidence of the prominent role of RCS in the pathogenesis of pneumoconiosis among contemporary US coal miners.


Assuntos
Minas de Carvão , Doenças Profissionais , Pneumoconiose , Humanos , Estados Unidos/epidemiologia , Doenças Profissionais/epidemiologia , Doenças Profissionais/etiologia , Doenças Profissionais/patologia , Dióxido de Silício/efeitos adversos , Poeira , Carvão Mineral/efeitos adversos , Fibrose
2.
Int Arch Occup Environ Health ; 93(3): 315-323, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31701235

RESUMO

PURPOSE: To examine associations between mine commodity such as coal, platinum, or diamonds and emphysema among South African miners at autopsy. METHODS: We examined the association between mine commodity and emphysema using the Pathology Automation (PATHAUT) database, 1975-2014. Exposure was characterized as longest tenure in each commodity. We constructed separate multivariable logistic regression models for black and white miners. Smoking was assessed in a sub-analysis of white miners. RESULTS: Among black miners, coal mining was significantly associated with increased odds of emphysema [OR = 2.39 (95% CI 1.86, 3.07)] when compared to gold mining. Asbestos was also associated with significantly increased odds of emphysema among black miners [OR = 1.47 (95% CI 1.01, 2.12)]. No associations between commodity and emphysema were observed among white miners. Cumulative years of exposure and age at death were significant predictors for emphysema for both black and white miners. Smoking was a significant predictor of emphysema in the sub-analysis of white miners with smoking information, but no effect of commodity was observed. CONCLUSIONS: We observed a significant association between coal mining and emphysema among black miners. Adverse health effects of coal mining are evidenced by more than twofold increase in emphysema among black coal miners compared to gold miners. This suggests that South African Coal miners are exposed to high dust concentrations or more damaging components compared to other commodities, resulting in elevated risk of emphysema.


Assuntos
Mineradores/estatística & dados numéricos , Doenças Profissionais/epidemiologia , Doenças Profissionais/etiologia , Exposição Ocupacional/efeitos adversos , Enfisema Pulmonar/epidemiologia , Enfisema Pulmonar/etiologia , Adulto , Autopsia , População Negra/estatística & dados numéricos , Indústria do Carvão Mineral , Humanos , Pessoa de Meia-Idade , Sistema de Registros , Fatores de Risco , África do Sul/epidemiologia , Elementos de Transição , População Branca/estatística & dados numéricos
3.
Occup Environ Med ; 75(11): 767-775, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29934377

RESUMO

OBJECTIVE: We investigated trends and determinants of pulmonary tuberculosis (PTB) in deceased South African miners. METHODS: Statutory autopsies are performed on miners for occupational lung disease compensation, irrespective of cause of death. Data were extracted from the PATHAUT (Pathology Automation System) autopsy database. PTB trends were analysed and explanatory variables (year of autopsy, age at death, gold employment duration, silicosis and HIV) were evaluated using binary logistic regression modelling. Analyses were stratified by population group because of racial differences in socioeconomic status, employment patterns and access to facilities for autopsies. The analyses were segmented to represent the pre-HIV (1975-1989), rapid HIV spread (1990-2004) and antiretroviral therapy (2005-2014) periods. RESULTS: The proportions of men with PTB at autopsy increased from 4.62% in 1975 to 27.18% in 2014 in black miners, and from 2.07% to 5.19% in white miners, with peaks in 2007 (43.12% and 9.51%, respectively). The magnitude and significance of adjusted ORs of determinants differed by population group and calendar period. PTB was largely associated with silicosis, increasing gold employment duration and year of autopsy (a surrogate for unmeasured confounders, such as unknown HIV status and tuberculosis transmission). CONCLUSIONS: Changes in PTB time trends and determinants reflect the complex social and political environment in which mining occurs. Silica dust reduction remains a key intervention for tuberculosis reduction, together with tuberculosis and HIV treatment and management. The autopsy data provide reliable information to monitor progress towards the achievement of industry and national targets to reduce tuberculosis.


Assuntos
Mineração , Doenças Profissionais/epidemiologia , Tuberculose Pulmonar/epidemiologia , Adulto , Idoso , Autopsia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Silicose/epidemiologia , África do Sul/epidemiologia
4.
Int Arch Occup Environ Health ; 91(8): 981-990, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30014161

RESUMO

PURPOSE: To determine the associations between exposure duration, measured by employment tenure, and emphysema presence and severity in black and white South African miners at autopsy. METHODS: We examined the association between mining tenure and emphysema presence or severity using the Pathology Automation (PATHAUT) database, 1975-2014. We used logistic regression models adjusted for age, tuberculosis, HIV status, and year of death. The effect of smoking on the presence and severity of emphysema was assessed in a sub-analysis of white miners. RESULTS: Mining tenure was significantly associated with increased odds of emphysema presence in black and white miners. For every 10-year increase in tenure, black miners had a 17% increase in odds of emphysema [ORblack = 1.17 (95% CI 1.12, 1.22)] and white miners had a 7% increase in odds of the disease [ORwhite = 1.07 (95% CI 1.04, 1.10)]. Tenure was significantly associated with emphysema severity among black miners [ORseverity = 1.16 (95% CI 1.06, 1.28)]. In a subset of white miners with smoking status, we found that for every 10 years of tenure, there is a significant increase in odds of emphysema presence and severity [ORpresence = 1.14 (95% CI 1.09, 1.19); ORseverity = 1.06 (95% CI 1.00, 1.10)] after adjusting for smoking. CONCLUSIONS: We observed a significant relationship between mining tenure and emphysema severity among South African miners in PATHAUT between 1975 and 2014. This relationship was evident in multi-variable analyses adjusted for smoking among white miners. Hazards from long term exposure to inhaled mineral dust leading to lung damage (silicosis, fibrosis, COPD) is evident and warrants further improvement of working conditions and prevention measures in South African mines especially for black workers. Further research is needed to determine if there is an effect of TB and HIV co-infection on the development of emphysema.


Assuntos
Emprego/estatística & dados numéricos , Mineração , Exposição Ocupacional/efeitos adversos , Pneumoconiose/etiologia , Enfisema Pulmonar/etiologia , Adulto , Idoso , Autopsia , População Negra/estatística & dados numéricos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/estatística & dados numéricos , Pneumoconiose/etnologia , Pneumoconiose/patologia , Enfisema Pulmonar/etnologia , Enfisema Pulmonar/patologia , Índice de Gravidade de Doença , Fumar/efeitos adversos , África do Sul/epidemiologia , Fatores de Tempo , População Branca/estatística & dados numéricos , Adulto Jovem
5.
Am J Ind Med ; 61(11): 877-885, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30239033

RESUMO

The purpose of this commentary is to bring the neglected phenomenon of subradiological silicosis and its implications to the attention of readers. We define subradiological silicosis as silicosis detectable on pathological examination of lung tissue but not visible radiologically. For extent of the phenomenon, we draw on a study using a large South African autopsy database of deceased miners and chest radiographs taken in life. At an International Labour Organization threshold of >1/0 only 43% of all pathologically detected cases were detected on chest radiograph, and only 62% of those classified on pathology as "moderate or marked" silicosis. Subradiological silicosis has a number of implications for research and practice: for dose-response studies of silicosis; for studies of the relationship between silica and conditions such as tuberculosis, lung cancer, and autoimmune disease, including the mechanistic role of fibrogenesis; for prognostication in silica exposed workers; and for workers' compensation criteria.


Assuntos
Pulmão/patologia , Radiografia/estatística & dados numéricos , Silicose/patologia , Autopsia , Bases de Dados Factuais , Diagnóstico Diferencial , Humanos , Pulmão/diagnóstico por imagem , Mineradores , Silicose/diagnóstico por imagem , África do Sul
6.
Am J Ind Med ; 59(4): 307-14, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26901656

RESUMO

BACKGROUND: South African miners have a statutory right to autopsies for occupational lung disease compensation. These autopsies also provide information for research and surveillance. METHODS: Cardio-respiratory organs are removed where miners die and are examined at the National Institute for Occupational Health. We extracted data from the PATHAUT database and described key demographic, exposure and disease trends (1975-2013). RESULTS: Of 109,101 autopsies, 72,348 (66.3%) were black, and 34,794 (31.9%) were white miners. Autopsies declined from over 3,000 (1975-1998) to 1,118 in 2013. Most were gold miners (74.0%). 78.6% black and 13.2% white miners died while in employment. Overall proportions of silicosis and pulmonary tuberculosis were 12.0% and 13.0% in black, and 20.5% and 2.4% in white miners, respectively. Disease increased over time. CONCLUSIONS: High levels of disease persist. Black ex-miners are underrepresented, indicating a need for strategies to improve awareness and provision of autopsy facilities in labor-sending areas.


Assuntos
Pneumopatias/mortalidade , Mineração/estatística & dados numéricos , Doenças Profissionais/mortalidade , Adulto , Autopsia/estatística & dados numéricos , Autopsia/tendências , População Negra/estatística & dados numéricos , Feminino , Ouro , Humanos , Pneumopatias/etiologia , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/etiologia , Silicose/etiologia , Silicose/mortalidade , África do Sul/epidemiologia , Tuberculose Pulmonar/etiologia , Tuberculose Pulmonar/mortalidade , População Branca/estatística & dados numéricos , Adulto Jovem
7.
J Hand Ther ; 28(2): 228-31; quiz 232, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25060856

RESUMO

This article describes how hand therapy for pediatric patients can be enhanced through the use of play with everyday items. Playful activities integrate purposeful hand skills of pinch, grasp and manipulation, while encouraging the child to fully participate in therapy and home programs. By referring to Takata's developmental hierarchy of play, therapists can design the sessions to include novel, fun and age appropriate activities. The author offers eight sample activities for specific therapy goals utilizing inexpensive, everyday items.


Assuntos
Terapia por Exercício/instrumentação , Força da Mão/fisiologia , Mãos/fisiologia , Jogos e Brinquedos , Adolescente , Criança , Pré-Escolar , Utensílios Domésticos , Humanos , Lactente , Recém-Nascido
8.
BMC Infect Dis ; 14: 3858, 2014 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-25528248

RESUMO

BACKGROUND: Tuberculosis (TB) mortality remains high across sub-Saharan Africa despite integration of TB and HIV/ART programmes. To inform programme design and service delivery, we estimated mortality by time from starting TB treatment. METHODS: Routinely collected data on TB treatment, vital status, and the timing and causes of death, were linked to cardio-respiratory autopsy data, from 1995-2008, from a cohort of male platinum miners in South Africa. Records were expanded into person-months at risk (pm). RESULTS: 4162 TB episodes were registered; 3170 men were treated for the first time and 833 men underwent retreatment. Overall, 509 men died, with a case fatality of 12.2% and mortality rate of 2.0/100 pm. Mortality was highest in the first month after starting TB treatment for first (2.3/100 pm) and retreatment episodes (4.8/100 pm). When stratified by HIV status, case fatality was higher in HIV positive men not on ART (first episode 14.0%; retreatment episode 26.2%) and those on ART (12.0%; 22.0%) than men of negative or unknown HIV status (2.6%; 3.6%). Mortality was also highest in the first month for each of these groups. Mortality risk factors included older age, previous TB, HIV, pulmonary TB, and diagnostic uncertainty. The proportion of deaths attributable to TB was consistently overestimated in clinical records versus cardio-respiratory autopsy. CONCLUSIONS: Programme mortality was highest in those with HIV and during the first month of TB treatment in all groups, and many deaths were not caused by TB. Resource allocation should prioritise TB prevention and accurate earlier diagnosis, recognise the role of HIV, and ensure effective clinical care in the early stages of TB treatment.


Assuntos
Infecções por HIV/mortalidade , Tuberculose Pulmonar/mortalidade , Adulto , Fatores Etários , Terapia Antirretroviral de Alta Atividade , Causas de Morte , Coinfecção/epidemiologia , Coinfecção/mortalidade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Retratamento , Fatores de Risco , África do Sul/epidemiologia , Fatores de Tempo , Tuberculose/epidemiologia , Tuberculose/mortalidade , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/epidemiologia
9.
Environ Sci Technol ; 48(16): 9043-52, 2014 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-25055204

RESUMO

Elevated levels of fecal indicator bacteria (FIB), including Escherichia coli and enterococci, trigger coastal beach advisories and signal public health risks. Solving FIB pollution in suburban coastal watersheds is challenging, as there are many potential sources. The Arroyo Burro watershed in Santa Barbara, CA is an example, with its popular, but chronically FIB-contaminated beach. To address, a microbial source tracking study was performed. Surface waters were sampled over 2 years, FIB were quantified, and DNA was analyzed for host-associated fecal markers. Surf zone FIB were only elevated when the coastal lagoon was discharging. Among the fecal sources into the lagoon, including upstream human sources and coastal birds, canines were the most important. Canine sources included input via upstream creek water, which decreased after creek-side residences were educated about proper pet waste disposal, and direct inputs to the lagoon and surf zone, where dog waste could have been tidally exchanged with the lagoon. Based on this study, canine waste can be an influential, yet controllable, fecal source to suburban coastal beaches.


Assuntos
Enterococcus/isolamento & purificação , Escherichia coli/isolamento & purificação , Fezes/microbiologia , Microbiologia da Água , Poluentes da Água/isolamento & purificação , Animais , Praias , Aves , California , DNA/análise , Cães , Monitoramento Ambiental , Fezes/química , Humanos
10.
Water Environ Res ; 86(6): 550-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25109201

RESUMO

Human fecal contamination of surface waters and drains is difficult to diagnose. DNA-based and chemical analyses of water samples can be used to specifically quantify human waste contamination, but their expense precludes routine use. We evaluated canine scent tracking, using two dogs trained to respond to the scent of municipal wastewater, as a field approach for surveying human fecal contamination. Fecal indicator bacteria, as well as DNA-based and chemical markers of human waste, were analyzed in waters sampled from canine scent-evaluated sites (urban storm drains and creeks). In the field, the dogs responded positively (70% and 100%) at sites for which sampled waters were then confirmed as contaminated with human waste. When both dogs indicated a negative response, human waste markers were absent. Overall, canine scent tracking appears useful for prioritizing sampling sites for which DNA-based and similarly expensive assays can confirm and quantify human waste contamination.


Assuntos
Cães/fisiologia , Fezes/microbiologia , Odorantes , Engenharia Sanitária , Esgotos , Animais , Monitoramento Ambiental , Humanos , Eliminação de Resíduos Líquidos , Poluição da Água/análise
11.
J Cell Sci ; 124(Pt 2): 280-91, 2011 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-21172801

RESUMO

Intrinsic antiviral resistance mediated by constitutively expressed cellular proteins is one arm of defence against virus infection. Promyelocytic leukaemia nuclear bodies (PML-NBs, also known as ND10) contribute to host restriction of herpes simplex virus type 1 (HSV-1) replication via mechanisms that are counteracted by viral regulatory protein ICP0. ND10 assembly is dependent on PML, which comprises several different isoforms, and depletion of all PML isoforms decreases cellular resistance to ICP0-null mutant HSV-1. We report that individual expression of PML isoforms I and II partially reverses the increase in ICP0-null mutant HSV-1 plaque formation that occurs in PML-depleted cells. This activity of PML isoform I is dependent on SUMO modification, its SUMO interaction motif (SIM), and each element of its TRIM domain. Detailed analysis revealed that the punctate foci formed by individual PML isoforms differ subtly from normal ND10 in terms of composition and/or Sp100 modification. Surprisingly, deletion of the SIM motif from PML isoform I resulted in increased colocalisation with other major ND10 components in cells lacking endogenous PML. Our observations suggest that complete functionality of PML is dependent on isoform-specific C-terminal sequences acting in concert.


Assuntos
Herpes Simples/metabolismo , Herpesvirus Humano 1/fisiologia , Proteínas Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Replicação Viral , Motivos de Aminoácidos , Linhagem Celular Tumoral , Regulação Viral da Expressão Gênica , Herpes Simples/virologia , Herpesvirus Humano 1/genética , Humanos , Proteínas Imediatamente Precoces/genética , Proteínas Imediatamente Precoces/metabolismo , Proteínas Nucleares/química , Proteínas Nucleares/genética , Proteína da Leucemia Promielocítica , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Sumoilação , Fatores de Transcrição/química , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/química , Proteínas Supressoras de Tumor/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
12.
PLoS Pathog ; 7(7): e1002123, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21779164

RESUMO

Components of promyelocytic leukaemia (PML) nuclear bodies (ND10) are recruited to sites associated with herpes simplex virus type 1 (HSV-1) genomes soon after they enter the nucleus. This cellular response is linked to intrinsic antiviral resistance and is counteracted by viral regulatory protein ICP0. We report that the SUMO interaction motifs of PML, Sp100 and hDaxx are required for recruitment of these repressive proteins to HSV-1 induced foci, which also contain SUMO conjugates and PIAS2ß, a SUMO E3 ligase. SUMO modification of PML and elements of its tripartite motif (TRIM) are also required for recruitment in cells lacking endogenous PML. Mutants of PML isoform I and hDaxx that are not recruited to virus induced foci are unable to reproduce the repression of ICP0 null mutant HSV-1 infection mediated by their wild type counterparts. We conclude that recruitment of ND10 components to sites associated with HSV-1 genomes reflects a cellular defence against invading pathogen DNA that is regulated through the SUMO modification pathway.


Assuntos
Núcleo Celular/metabolismo , DNA Viral/metabolismo , Genoma Viral , Herpes Simples/metabolismo , Proteínas Repressoras/metabolismo , Proteína SUMO-1/metabolismo , Simplexvirus/metabolismo , Motivos de Aminoácidos , Antígenos Nucleares/genética , Antígenos Nucleares/metabolismo , Autoantígenos/genética , Autoantígenos/metabolismo , Núcleo Celular/genética , Núcleo Celular/virologia , DNA Viral/genética , Células HEK293 , Herpes Simples/genética , Humanos , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteína da Leucemia Promielocítica , Proteínas Inibidoras de STAT Ativados/genética , Proteínas Inibidoras de STAT Ativados/metabolismo , Proteínas Repressoras/genética , Proteína SUMO-1/genética , Simplexvirus/genética , Sumoilação/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
13.
Arch Pathol Lab Med ; 2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37852172

RESUMO

CONTEXT.­: The pathology of coal workers' pneumoconiosis (CWP) and its most severe form-progressive massive fibrosis (PMF)-in US coal miners has changed in recent years. Severe disease is occurring in younger miners and has been linked to an increase in silica dust exposure. OBJECTIVE.­: To update the description of the pathologic features of CWP in contemporary miners compared to historical miners. DESIGN.­: This study is a retrospective expert classification of lung tissue from 85 historical and contemporary coal miners with PMF. Significant pathologic features were scored by using a standardized instrument with consensus achieved for major findings, including newly defined categories of PMF as coal-type, mixed-type, and silica-type. RESULTS.­: Pathologic features associated with silica dust exposure, including silica-type PMF, mineral dust alveolar proteinosis (MDAP), and immature (early stage) silicotic nodules were increased in contemporary miners. Detailed descriptions of the pathology of contemporary CWP with illustrative figures are provided. CONCLUSIONS.­: Silica-related pathologies are more common in contemporary miners. Severe forms of CWP can be detected by subtyping PMF lesions (if present) or by identification of mature and immature silicotic nodules, coal mine dust-related alveolar proteinosis, and severe inflammation in coal miners' lungs. Silica-type PMF cases showed significantly higher levels of MDAP than either mixed- or coal-type PMF (P < .001). High profusion of birefringent silica/silicate particles was observed more frequently in cases with immature (early stage) silicotic nodules (P = .04). Severe inflammation was also significantly increased in contemporary miners (P = .03). Our findings underscore the urgent need to revise current exposure limits and monitoring of respirable crystalline silica in US coal mines.

14.
J Occup Environ Med ; 65(4): 315-320, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36730599

RESUMO

OBJECTIVE: To characterize differences in mining jobs and tenure between contemporary (born 1930+, working primarily with modern mining technologies) and historic coal miners with progressive massive fibrosis (PMF). METHODS: We classified jobs as designated occupations (DOs) and non-DOs based on regulatory sampling requirements. Demographic, occupational characteristics, and histopathological PMF type were compared between groups. RESULTS: Contemporary miners ( n = 33) had significantly shorter mean total (30.4 years vs 37.1 years, P = 0.0006) and underground (28.8 years vs 35.8 years, P = 0.001) mining tenure compared with historic miners ( n = 289). Silica-type PMF was significantly more common among miners in non-DOs (30.1% vs 15.8%, P = 0.03) and contemporary miners (58.1% vs 15.2%, P < 0.0001). CONCLUSIONS: Primary jobs changed over time with the introduction of modern mining technologies and likely changed exposures for workers. Elevated crystalline silica exposures are likely in non-DOs and require attention.


Assuntos
Minas de Carvão , Exposição Ocupacional , Pneumoconiose , Humanos , Ocupações , Dióxido de Silício , Fibrose , Carvão Mineral , Exposição Ocupacional/efeitos adversos
15.
BMC Struct Biol ; 12: 16, 2012 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-22747601

RESUMO

BACKGROUND: S100 proteins are a family of small, EF-hand containing calcium-binding signaling proteins that are implicated in many cancers. While the majority of human S100 proteins share 25-65% sequence similarity, S100A7 and its recently identified paralog, S100A15, display 93% sequence identity. Intriguingly, however, S100A7 and S100A15 serve distinct roles in inflammatory skin disease; S100A7 signals through the receptor for advanced glycation products (RAGE) in a zinc-dependent manner, while S100A15 signals through a yet unidentified G-protein coupled receptor in a zinc-independent manner. Of the seven divergent residues that differentiate S100A7 and S100A15, four cluster in a zinc-binding region and the remaining three localize to a predicted receptor-binding surface. RESULTS: To investigate the structural and functional consequences of these divergent clusters, we report the X-ray crystal structures of S100A15 and S100A7D24G, a hybrid variant where the zinc ligand Asp24 of S100A7 has been substituted with the glycine of S100A15, to 1.7 Å and 1.6 Å resolution, respectively. Remarkably, despite replacement of the Asp ligand, zinc binding is retained at the S100A15 dimer interface with distorted tetrahedral geometry and a chloride ion serving as an exogenous fourth ligand. Zinc binding was confirmed using anomalous difference maps and solution binding studies that revealed similar affinities of zinc for S100A15 and S100A7. Additionally, the predicted receptor-binding surface on S100A7 is substantially more basic in S100A15 without incurring structural rearrangement. CONCLUSIONS: Here we demonstrate that S100A15 retains the ability to coordinate zinc through incorporation of an exogenous ligand resulting in a unique zinc-binding site among S100 proteins. The altered surface chemistry between S100A7 and S100A15 that localizes to the predicted receptor binding site is likely responsible for the differential recognition of distinct protein targets. Collectively, these data provide novel insight into the structural and functional consequences of the divergent surfaces between S100A7 and S100A15 that may be exploited for targeted therapies.


Assuntos
Receptores de Superfície Celular/metabolismo , Proteínas S100/química , Proteínas S100/metabolismo , Zinco/metabolismo , Sequência de Aminoácidos , Substituição de Aminoácidos/genética , Sítios de Ligação , Complexo do Signalossomo COP9 , Cristalografia por Raios X , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Modelos Moleculares , Dados de Sequência Molecular , Peptídeo Hidrolases/metabolismo , Ligação Proteica , Receptor para Produtos Finais de Glicação Avançada , Receptores Imunológicos/metabolismo , Proteína A7 Ligante de Cálcio S100 , Propriedades de Superfície
16.
Water Res ; 221: 118781, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35759849

RESUMO

Fecal sources to recreational surf zone waters should be identified to protect public health. While watershed origins of human and other fecal sources are often discoverable by quantitative polymerase chain reaction (qPCR) of fecal markers using spatially stratified samples, similarly assessing wastewater treatment plant (WWTP) outfall and other offshore contributions to surf zones is challenged by individual marker fate and transport. Here, bacterial communities were assessed for relatedness between all hypothesized fecal sources and surf zone waters for two urban California recreational beaches, by sequencing genes encoding 16S rRNA and analyzing data using SourceTracker and FEAST. Ambient marine bacterial communities dominated the surf zone, while fecal (human, dog, or gull) or wastewater (sewage or treated WWTP effluent) bacterial communities were present at low proportions and those from recycled water were absent. Based on the relative abundances of bacterial genera specifically associated with human feces, the abundances of HF183 in bacterial community sequences, and FEAST and SourceTracker results when benchmarked to HF183, the major sources of HF183 to surf zone waters were human feces and treated WWTP effluent. While surf zone sequence proportions from human sources (feces, sewage and treated WWTP effluent) appeared uncorrelated to previously obtained qPCR HF183 results, the proportions of human fecal and potential human pathogen sequences in surf zone waters were elevated when there were more swimmers (i.e. during weekday afternoons, holidays and busy weekends, and race events), thus confirming previously-published qPCR-based conclusions that bather shedding contributed low levels of human fecal contamination. Here, bacterial community sequencing also showed evidence that treated WWTP effluent from an offshore outfall was entering the surf zone, thereby resolving a prior uncertainty. Thus, bacterial community sequencing not only confirms qPCR HF183-based human marker detections, but further allows for confirming fecal sources for which individual marker quantification results can be equivocal.


Assuntos
Praias , Monitoramento Ambiental , Fezes , Esgotos , Microbiologia da Água , Animais , Bactérias/genética , Charadriiformes , Cães , Monitoramento Ambiental/métodos , Fezes/microbiologia , Humanos , RNA Ribossômico 16S/genética , Esgotos/microbiologia , Purificação da Água
17.
Ann Am Thorac Soc ; 19(9): 1469-1478, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35353671

RESUMO

Rationale: The reasons for resurgent coal workers' pneumoconiosis and its most severe forms, rapidly progressive pneumoconiosis and progressive massive fibrosis (PMF), in the United States are not yet fully understood. Objectives: To compare the pathologic and mineralogic features of contemporary coal miners with severe pneumoconiosis with those of their historical counterparts. Methods: Lung pathology specimens from 85 coal miners with PMF were included for evaluation and analysis. We compared the proportion of cases with pathologic and mineralogic findings in miners born between 1910 and 1930 (historical) with those in miners born in or after 1930 (contemporary). Results: We found a significantly higher proportion of silica-type PMF (57% vs. 18%; P < 0.001) among contemporary miners compared with their historical counterparts. Mineral dust alveolar proteinosis was also more common in contemporary miners compared with their historical counterparts (70% vs. 37%; P < 0.01). In situ mineralogic analysis showed that the percentage (26.1% vs. 17.8%; P < 0.01) and concentration (47.3 × 108 vs. 25.8 × 108 particles/cm3; P = 0.036) of silica particles were significantly greater in specimens from contemporary miners compared with their historical counterparts. The concentration of silica particles was significantly greater when silica-type PMF, mineral dust alveolar proteinosis, silicotic nodules, or immature silicotic nodules were present (P < 0.05). Conclusions: Exposure to respirable crystalline silica appears causal in the unexpected surge of severe disease in contemporary miners. Our findings underscore the importance of controlling workplace silica exposure to prevent the disabling and untreatable adverse health effects afflicting U.S. coal miners.


Assuntos
Antracose , Minas de Carvão , Exposição Ocupacional , Pneumoconiose , Proteinose Alveolar Pulmonar , Antracose/epidemiologia , Carvão Mineral , Poeira , Humanos , Exposição Ocupacional/efeitos adversos , Pneumoconiose/epidemiologia , Prevalência , Dióxido de Silício/efeitos adversos , Estados Unidos/epidemiologia
18.
J Virol ; 84(9): 4252-63, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20181717

RESUMO

The herpes simplex virus type 1 (HSV-1) UL25 gene encodes a minor capsid protein, pUL25, that is essential for packaging the full-length viral genome. Six regions which contain disordered residues have been identified in the high-resolution structure of pUL25. To investigate the significance of these flexible regions, a panel of plasmids was generated encoding mutant proteins, with each member lacking the disordered residues in one of the six regions. In addition, UL25 constructs were produced, which specified proteins that contained missense mutations individually affecting two of the four regions on the surface of pUL25 predicted from evolutionary trace analysis to be important in protein-protein interactions. The impacts of these mutations on viral DNA packaging, virus assembly, and growth were examined. Of the nine mutant proteins analyzed, five failed to complement the growth of a UL25 deletion mutant in Vero cells. These noncomplementing proteins fell into three classes. Proteins in one class did not alter the DNA packaging phenotype of an HSV-1 UL25 deletion mutant, whereas proteins from the other two classes allowed the UL25 null mutant to package full-length viral DNA. Subsequent analysis of the latter classes of mutant proteins demonstrated that one class enabled the null virus to release enveloped virus particles from U2OS cells, whereas the other class prevented egress of mature HSV-1 capsids from the nucleus. These findings reveal a new role for pUL25 in virion assembly, consistent with its flexible structure and location on the capsid.


Assuntos
Proteínas do Capsídeo/fisiologia , Empacotamento do DNA , Herpesvirus Humano 1/fisiologia , Montagem de Vírus , Liberação de Vírus , Animais , Proteínas do Capsídeo/genética , Linhagem Celular , Chlorocebus aethiops , DNA Viral/metabolismo , Deleção de Genes , Teste de Complementação Genética , Herpesvirus Humano 1/genética , Humanos , Microscopia Eletrônica de Transmissão , Modelos Moleculares , Mutagênese Sítio-Dirigida , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Mutação de Sentido Incorreto , Estrutura Terciária de Proteína , Vírion/ultraestrutura
19.
Appl Environ Microbiol ; 77(2): 627-33, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21097584

RESUMO

Monitoring microbiological water quality is important for protecting water resources and the health of swimmers. Routine monitoring relies on cultivating fecal indicator bacteria (FIB), frequently using defined substrate technology. Defined substrate technology is designed to specifically enrich for FIB, but a complete understanding of the assay microbiology requires culture-independent analysis of the enrichments. This study aimed to identify bacteria in positive wells of Colilert and Enterolert Quanti-Tray/2000 (IDEXX Laboratories) FIB assays in environmental water samples and to quantify the degree of false-positive results for samples from an urban creek by molecular methods. Pooled Escherichia coli- and Enterococcus-positive Quanti-Tray/2000 enrichments, either from urban creek dry weather flow or municipal sewage, harbored diverse bacterial populations based on 16S rRNA gene sequences and terminal restriction fragment length polymorphism analyses. Target taxa (coliforms or enterococci) and nontarget taxa (Vibrio spp., Shewanella spp., Bacteroidetes, and Clostridium spp.) were identified in pooled and individual positive Colilert and Enterolert wells based on terminal restriction fragments that were in common with those generated in silico from clone sequences. False-positive rates of between 4 and 23% occurred for the urban creek samples, based on the absence of target terminal restriction fragments in individual positive wells. This study suggests that increased selective inhibition of nontarget bacteria could improve the accuracy of the Colilert and Enterolert assays.


Assuntos
Técnicas Bacteriológicas/métodos , Enterobacteriaceae/isolamento & purificação , Monitoramento Ambiental/métodos , Fezes/microbiologia , Água Doce/microbiologia , Impressões Digitais de DNA , DNA Bacteriano/química , DNA Bacteriano/genética , Enterobacteriaceae/classificação , Enterobacteriaceae/genética , Reações Falso-Positivas , Dados de Sequência Molecular , Polimorfismo de Fragmento de Restrição , RNA Ribossômico 16S/genética , Sensibilidade e Especificidade , Análise de Sequência de DNA , Esgotos/microbiologia
20.
Microb Ecol ; 62(3): 574-83, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21617896

RESUMO

Microbiological contamination from runoff is a human health concern in urbanized coastal environments, but the contamination sources are often unknown. This study quantified fecal indicator bacteria and compared the distributions of human-specific genetic markers and bacterial community composition during dry and wet weather in urban creeks draining two neighboring watersheds in Santa Barbara, CA. In a prior study conducted during exclusively dry weather, the creeks were contaminated with human waste as indicated by elevated numbers of the human-specific Bacteroidales marker HF183 (Sercu et al. in Environ Sci Technol 43:293-298, 2009). During the storm, fecal indicator bacterial numbers and loads increased orders of magnitude above dry weather conditions. Moreover, bacterial community composition drastically changed during rainfall and differed from dry weather flow by (1) increased bacterial diversity, (2) reduced spatial heterogeneity within and between watersheds, and (3) clone library sequences more related to terrestrial than freshwater taxa. Finally, the spatial patterns of human-associated genetic markers (HF183 and Methanobrevibacter smithii nifH gene) changed during wet weather, and the contribution of surface soils to M. smithii nifH gene detection was suspected. The increased fecal indicator bacteria numbers during wet weather were likely associated with terrestrial sources, instead of human waste sources that dominated during dry weather flow.


Assuntos
Bactérias/isolamento & purificação , Cidades , Microbiologia da Água , Qualidade da Água , Bactérias/genética , California , Contagem de Colônia Microbiana , Fezes/microbiologia , Água Doce/microbiologia , Marcadores Genéticos , Humanos , Methanobrevibacter/genética , Methanobrevibacter/isolamento & purificação , Polimorfismo de Fragmento de Restrição , Chuva/microbiologia , Movimentos da Água , Poluição da Água/análise
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