213 research outputs found

    The Black Lung Benefits Act: An Operator\u27s Perspective

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    To be successful, attorneys must acquire certain basic skills and knowledge in their respective areas of expertise. Additionally, attorneys must participate in continuing legal education to maintain these basic skills and knowledge. This is especially true for federal black lung attorneys due to the dynamic nature of the law in this area. Federal black lung law has changed dramatically since the orginial enactment of Title IV of the Federal Coal Mine Health and Safety Act of 1969. Since its passage in December 1969, the Act has been substantially amended twice, first by the Black Lung Benefits Act of 1972 (BLBA), and more recently, by the Black Lung Benefits Reform Act of 1977 (BLBRA) Each of these legislative enactments have been followed by the enactment of voluminous regulations seeking to interpret and clarify the legislative intent of Congress. Furthermore, responsibility for the administration of the Act has been transferred from the Department of Human Services to the Department of Labor. With this transfer, claims adjudication procedures have changed dramatically in that what formerly was a non-adversarial action by a claimant against the Federal Disability Insurance Trust Fund, has been transformed into a full adversarial proceeding involving private operator liability. Apart from these developments in the law and its administration, the science and practice of occupational lung disease medicine here in the United States has experienced great advances during the past ten years. These medical advances have had a great impact upon the Act. To represent a client effectively in light of this state of change, the federal black lung practitioner must have command of the facts of his or her case as well as a solid foundation of knowledge in the Act, its regulations, and pulmonary medicine. The typical black lung case presents issues of law; issues of fact; medical issues; and issues which are a mixture of law, fact, and medicine. To provide within the pages of a single article all the basics that the skilled attorney needs to know about each of these issues is an ambitious undertaking; yet, this article will seek to identify the basic knowledge which the federal black lung practitioner should command with respect to each issue. To facilitate understanding and to provide adequate coverage of each of these issues, this article has been organized into two general sections. Part I discusses the Act and its permanent regulations, and Part II discusses black lung pulmonary medicine. The footnotes, especially those in the section on medicine, have been chosen for further reading by the black lung practitioner

    On the Cusp: A Study of Macro- & Microwear in Middle Woodland & Mississippian Skeletal Samples from the Lower Midwest

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    poster abstractStudies of dental macro- and microwear are emerging as complimentary lines of evidence to archaeological research, enabling scholars to track changes in the mode of subsistence over long and short periods. These tooth wear studies simultaneously allow for analyses within and between age and sex cohorts, providing surrogate measures of a population’s dietary diversity. The current study examines dental wear for two Pre-Columbian samples from the Midcontinental United States. The first (n = 10) is from the Middle Woodland period Mann (12Po2) site, which is located on the Ohio River in southwestern Indiana. Recent radiocarbon dating conducted as part of the current research indicates the site was utilized between AD 127 and 259. Paleoethnobotanical research demonstrates that Middle Woodland people engaged in hunting and gathering, as well as a form of low-level food production that relied on indigenous starchy and oily seeds. The second sample (n = 20) is from the Mississippian period Orendorf (11F107) site in the Central Illinois River Valley. Previous radiometric assays indicate that the site was occupied between AD 1175 and 1250 with the site’s inhabitants taking part in a broad-scale subsistence change to maize agriculture. While research is ongoing and data will be forthcoming for the Mann site, measures of microwear complexity (1.49 asfc) and anisotropy (0.0032 epLsar1.8) from Orendorf reveal a diet that was rough with a low level of orientation between features on the occlusal surfaces of molars. Contrary to previous studies, individuals from Orendorf are atypical among late prehistoric, Midcontinental agriculturalists with a rougher diet more characteristic of preceding foragers or horticulturalists. In a comparison to a worldwide database, dietary roughness for Orendorf is comparable to Early Bronze Age farmers from England; however, the anisotropy value for Orendorf clusters with the Mebrak buckwheat farmers of Nepal and Neolithic samples from Israel

    Molecular Cell Short Article trans-Splicing to Spliceosomal U2 snRNA Suggests Disruption of Branch Site-U2 Pairing during Pre-mRNA Splicing

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    SUMMARY Pairing between U2 snRNA and the branch site of spliceosomal introns is essential for spliceosome assembly and is thought to be required for the first catalytic step of splicing. We have identified an RNA comprising the 5 0 end of U2 snRNA and the 3 0 exon of the ACT1-CUP1 reporter gene, resulting from a trans-splicing reaction in which a 5 0 splice site-like sequence in the universally conserved branch site-binding region of U2 is used in trans as a 5 0 splice site for both steps of splicing in vivo. Formation of this product occurs in functional spliceosomes assembled on reporter genes whose 5 0 splice sites are predicted to bind poorly at the spliceosome catalytic center. Multiple spatially disparate splice sites in U2 can be used, calling into question both the fate of its pairing to the branch site and the details of its role in splicing catalysis

    Endogenous U2.U5.U6 snRNA complexes in S. pombe are intron lariat spliceosomes

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    Excision of introns from pre-mRNAs is mediated by the spliceosome, a multi-megadalton complex consisting of U1, U2, U4/U6, and U5 snRNPs plus scores of associated proteins. Spliceosome assembly and disassembly are highly dynamic processes involving multiple stable intermediates. In this study, we utilized a split TAP-tag approach for large-scale purification of an abundant endogenous U2.U5.U6 complex from Schizosaccharomyces pombe. RNAseq revealed this complex to largely contain excised introns, indicating that it is primarily ILS (intron lariat spliceosome) complexes. These endogenous ILS complexes are remarkably resistant to both high-salt and nuclease digestion. Mass spectrometry analysis identified 68, 45, and 43 proteins in low-salt-, high-salt-, and micrococcal nuclease-treated preps, respectively. The protein content of a S. pombe ILS complex strongly resembles that previously reported for human spliced product (P) and Saccharomyces cerevisiae ILS complexes assembled on single pre-mRNAs in vitro. However, the ATP-dependent RNA helicase Brr2 was either substoichiometric in low-salt preps or completely absent from high-salt and MNase preps. Because Brr2 facilitates spliceosome disassembly, its relative absence may explain why the ILS complex accumulates logarithmically growing cultures and the inability of S. pombe extracts to support in vitro splicing

    Redes de coautoría de investigación en salud pública en Santander

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    Introduction: Although a good deal of research in public health has been performed, large inequalities still exist in health. It is necessary to know how knowledge is generated and disseminated to the public in order for research to reach decision-makers.Objective: To characterize public health research networks in Santander, Colombia.Materials and methods: Analysis of social networks based on co-authorship of scientific publications by researchers living in Santander in 2012. Researchers were identified using a “snowball” technique. The publications search was conducted using national and international databases. The density and average geodesic distance of networks were calculated, as was the size, pairs, brokers and homophily of egocentric networks.Results: There were 531 researchers. Most worked in epidemiology (77.59%), and in more than one thematic field. The network density was 0.0058 and the average geodesic distance was 4.418. Several indicators suggested that the most cohesive egocentric networks were those in which researches investigated more than in one knowledge area or in epidemiology. Homophily was lower for health systems, biostatistics and social and behavioral sciences, as well as private hospitals and the public university.Conclusions: The network structure suggests a growth phase in research and a predominance of epidemiology. Other public health areas need strengthening so as to better address the health needs of the state.Introducción. Aunque hay mucha investigación relacionada con la salud pública, aún persisten grandes desigualdades en este campo. Es necesario conocer cómo se genera el conocimiento y cómo se divulga al público para acercar la investigación a los tomadores de decisiones.Objetivo. Caracterizar las redes de investigación en salud pública en Santander, Colombia.Materiales y métodos. Se analizaron las redes sociales con base en la coautoría de publicaciones científicas de investigadores residentes en Santander durante el 2012. Se identificó a los investigadores mediante el llamado muestreo de “bola de nieve”. Las publicaciones se buscaron en bases de datos nacio-nales e internacionales. Se calcularon la densidad y la distancia geodésica promedio de la red, así como el tamaño, las parejas, el agente conector (broker) y la ‘homofilia’ (afinidad) de las redes egocéntricas.Resultados. Se detectaron 531 investigadores, la mayoría en epidemiología (77,59 %) y en más de un área temática. La densidad de la red fue de 0,0058 y, la distancia geodésica promedio, de 4,418. Varios indicadores sugirieron que las redes egocéntricas más cohesionadas fueron las de quienes investigan en más de un área del conocimiento o en epidemiología. La ‘homofilia’ fue menor en sistemas de salud, bioestadística y ciencias sociales y del comportamiento, así como en instituciones hospitalarias privadas y en la universidad pública.Conclusiones. La estructura de la red sugiere una fase de crecimiento de la investigación y un predominio de la aproximación epidemiológica. Es necesario fortalecer las demás áreas de salud pública para mejorar la respuesta ante las necesidades de salud del departamento

    Isoforms of U1-70k control subunit dynamics in the human spliceosomal U1 snRNP

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    Most human protein-encoding genes contain multiple exons that are spliced together, frequently in alternative arrangements, by the spliceosome. It is established that U1 snRNP is an essential component of the spliceosome, in human consisting of RNA and ten proteins, several of which are post- translationally modified and exist as multiple isoforms. Unresolved and challenging to investigate are the effects of these post translational modifications on the dynamics, interactions and stability of the particle. Using mass spectrometry we investigate the composition and dynamics of the native human U1 snRNP and compare native and recombinant complexes to isolate the effects of various subunits and isoforms on the overall stability. Our data reveal differential incorporation of four protein isoforms and dynamic interactions of subunits U1-A, U1-C and Sm-B/B’. Results also show that unstructured post- ranslationally modified C-terminal tails are responsible for the dynamics of Sm-B/B’ and U1-C and that their interactions with the Sm core are controlled by binding to different U1-70k isoforms and their phosphorylation status in vivo. These results therefore provide the important functional link between proteomics and structure as well as insight into the dynamic quaternary structure of the native U1 snRNP important for its function.This work was funded by: BBSRC (OVM), BBSRC and EPSRC (HH and NM), EU Prospects (HH), European Science Foundation (NM), the Royal Society (CVR), and fellowship from JSPS and HFSP (YM and DAPK respectively)

    Evolutionary Convergence on Highly-Conserved 3′ Intron Structures in Intron-Poor Eukaryotes and Insights into the Ancestral Eukaryotic Genome

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    The presence of spliceosomal introns in eukaryotes raises a range of questions about genomic evolution. Along with the fundamental mysteries of introns' initial proliferation and persistence, the evolutionary forces acting on intron sequences remain largely mysterious. Intron number varies across species from a few introns per genome to several introns per gene, and the elements of intron sequences directly implicated in splicing vary from degenerate to strict consensus motifs. We report a 50-species comparative genomic study of intron sequences across most eukaryotic groups. We find two broad and striking patterns. First, we find that some highly intron-poor lineages have undergone evolutionary convergence to strong 3′ consensus intron structures. This finding holds for both branch point sequence and distance between the branch point and the 3′ splice site. Interestingly, this difference appears to exist within the genomes of green alga of the genus Ostreococcus, which exhibit highly constrained intron sequences through most of the intron-poor genome, but not in one much more intron-dense genomic region. Second, we find evidence that ancestral genomes contained highly variable branch point sequences, similar to more complex modern intron-rich eukaryotic lineages. In addition, ancestral structures are likely to have included polyT tails similar to those in metazoans and plants, which we found in a variety of protist lineages. Intriguingly, intron structure evolution appears to be quite different across lineages experiencing different types of genome reduction: whereas lineages with very few introns tend towards highly regular intronic sequences, lineages with very short introns tend towards highly degenerate sequences. Together, these results attest to the complex nature of ancestral eukaryotic splicing, the qualitatively different evolutionary forces acting on intron structures across modern lineages, and the impressive evolutionary malleability of eukaryotic gene structures

    Modelling Reveals Kinetic Advantages of Co-Transcriptional Splicing

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    Messenger RNA splicing is an essential and complex process for the removal of intron sequences. Whereas the composition of the splicing machinery is mostly known, the kinetics of splicing, the catalytic activity of splicing factors and the interdependency of transcription, splicing and mRNA 3′ end formation are less well understood. We propose a stochastic model of splicing kinetics that explains data obtained from high-resolution kinetic analyses of transcription, splicing and 3′ end formation during induction of an intron-containing reporter gene in budding yeast. Modelling reveals co-transcriptional splicing to be the most probable and most efficient splicing pathway for the reporter transcripts, due in part to a positive feedback mechanism for co-transcriptional second step splicing. Model comparison is used to assess the alternative representations of reactions. Modelling also indicates the functional coupling of transcription and splicing, because both the rate of initiation of transcription and the probability that step one of splicing occurs co-transcriptionally are reduced, when the second step of splicing is abolished in a mutant reporter
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