Early Palaeozoic ocean anoxia and global warming driven by the evolution of shallow burrowing

The evolution of burrowing animals forms a defining event in the history of the Earth. It has been hypothesised that the expansion of seafloor burrowing during the Palaeozoic altered the biogeochemistry of the oceans and atmosphere. However, whilst potential impacts of bioturbation on the individual phosphorus, oxygen and sulphur cycles have been considered, combined effects have not been investigated, leading to major uncertainty over the timing and magnitude of the Earth system response to the evolution of bioturbation. Here we integrate the evolution of bioturbation into the COPSE model of global biogeochemical cycling, and compare quantitative model predictions to multiple geochemical proxies. Our results suggest that the advent of shallow burrowing in the early Cambrian contributed to a global low-oxygen state, which prevailed for ~100 million years. This impact of bioturbation on global biogeochemistry likely affected animal evolution through expanded ocean anoxia, high atmospheric CO2 levels and global warming

Genetic polymorphisms in TNF genes and tuberculosis in North Indians

<p>Abstract</p> <p>Background</p> <p>Pulmonary tuberculosis, the most common clinical form of mycobacterial diseases, is a granulomatous disease of the lungs caused by <it>Mycobaterium tuberculosis</it>. A number of genes have been identified in studies of diverse origins to be important in tuberculosis. Of these, both tumor necrosis factor α (TNF-α) and lymphotoxin α (LT-α) play important immunoregulatory roles.</p> <p>Methods</p> <p>To investigate the association of <it>TNF </it>polymorphisms with tuberculosis in the Asian Indians, we genotyped five potentially functional promoter polymorphisms in the <it>TNFA </it>gene and a <it>LTA_NcoI </it>polymorphism (+252 position) of the <it>LTA </it>gene in a clinically well-defined cohort of North-Indian patients with tuberculosis (N = 185) and their regional controls (N = 155). Serum TNF-α (sTNF-α) levels were measured and correlated with genotypes and haplotypes.</p> <p>Results</p> <p>The comparison of the allele frequencies for the various loci investigated revealed no significant differences between the tuberculosis patients and controls. Also, when the patients were sub-grouped into minimal, moderately advanced and far advanced disease on the basis of chest radiographs, TST and the presence/absence of cavitary lesions, none of the polymorphisms showed a significant association with any of the patient sub-groups. Although a significant difference was observed in the serum TNF-α levels in the patients and the controls, none of the investigated polymorphisms were found to affect the sTNF-α levels. Interestingly, it was observed that patients with minimal severity were associated with lower log sTNF-α levels when compared to the patients with moderately advanced and far advanced severity. However, none of these differences were found to be statistically significant. Furthermore, when haplotypes were analyzed, no significant difference was observed.</p> <p>Conclusions</p> <p>Thus, our findings exclude the <it>TNF </it>genes as major risk factor for tuberculosis in the North Indians.</p

What are the evolutionary constraints on larval growth in a trophically transmitted parasite?

For organisms with a complex life cycle, a large larval size is generally beneficial, but it may come at the expense of prolonged development. Individuals that grow fast may avoid this tradeoff and switch habitats at both a larger size and younger age. A fast growth rate itself can be costly, however, as it requires greater resource intake. For parasites, fast larval growth is assumed to increase the likelihood of host death before transmission to the next host occurs. Using the tapeworm Schistocephalus solidus in its copepod first intermediate host, I investigated potential constraints in the parasite’s larval life history. Fast-growing parasites developed infectivity earlier, indicating there is no functional tradeoff between size and developmental time. There was significant growth variation among full-sib worm families, but fast-growing sibships were not characterized by lower host survival or more predation-risky host behavior. Parental investment also had little effect on larval growth rates. The commonly assumed constraints on larval growth and development were not observed in this system, so it remains unclear what prevents worms from exploiting their intermediate hosts more aggressively

Tipping points in the dynamics of speciation.

Speciation can be gradual or sudden and involve few or many genetic changes. Inferring the processes generating such patterns is difficult, and may require consideration of emergent and non-linear properties of speciation, such as when small changes at tipping points have large effects on differentiation. Tipping points involve positive feedback and indirect selection stemming from associations between genomic regions, bi-stability due to effects of initial conditions and evolutionary history, and dependence on modularity of system components. These features are associated with sudden 'regime shifts' in other cellular, ecological, and societal systems. Thus, tools used to understand other complex systems could be fruitfully applied in speciation research

Personal non-commercial use only

ABSTRACT. Objective. To summarize the work performed by the Outcome Measures in Rheumatology (OMERACT) Ultrasound (US) Working Group on the validation of US as a potential outcome measure in gout. Methods. Based on the lack of definitions, highlighted in a recent literature review on US as an outcome tool in gout, a series of iterative exercises were carried out to obtain consensus-based definitions on US elementary components in gout using a Delphi exercise and subsequently testing these definitions in static images and in patients with proven gout. Cohen&apos;s κ was used to test agreement, and values of 0-0.20 were considered poor, 0.20-0.40 fair, 0.40-0.60 moderate, 0.60-0.80 good, and 0.80-1 excellent. Results. With an agreement of &gt; 80%, consensus-based definitions were obtained for the 4 elementary lesions highlighted in the literature review: tophi, aggregates, erosions, and double contour (DC). In static images interobserver reliability ranged from moderate to almost perfect, and similar results were found for the intrareader reliability. In patients the intraobserver agreement was good for all lesions except DC (moderate). The Outcome Measures in Rheumatology (OMERACT) US Working Group (Appendix 1) developed a gout subgroup with the purpose of validating US as an imaging tool for gout. If this objective is achieved, US may be implemented as an outcome measure in gout. Is Ultrasound a Validated Outcome Measure in Gout? In 2013, a systematic literature review was published evaluating US as an outcome tool in gout and asymptomatic hyperuricemia 10 . The report found 18 out of 67 articles published since 1975 to be eligible for review. Described in the literature were 4 main pathologies related solely to gout: tophi, double contour sign (DC), soft tissue abnormalities, and bony lesions. The review highlighted that US was able to detect tophi using magnetic resonance imaging (MRI) as a gold standard, and this measure was found sensitive to change. The DC is an articular cartilage abnormality related to the deposition of crystals on the surface of the hyaline cartilage, which seemed specific to gout, with excellent inter-reader reliability and sensitive to change (the latter only in a very small patient population). Soft tissue pathology such as intrasynovial hyperechogenicity may be indicative of gout. US was less sensitive than MRI for diagnosing erosions (bony lesions) but more sensitive than conventional radiography, as is also known from rheumatoid arthritis studies Criterion and construct validity were assessed only for tophi, and overall there was a lack of consensus on the definitions of the 4 elementary lesions and their validity according to the OMERACT filter 13 . Current Limitations of US in Gout Assessment Despite clear interest in this imaging technique for the management of gout, the literature review clearly pointed to a lack of clear US definitions for the main 4 elementary lesions identified: tophi, DC, soft tissue hyperechogenicity (punctuate crystal aggregates), and bony lesions (erosions). This lack of consensus-based definitions impairs the ability to validate US according to the OMERACT filter and hampers widespread use of US in therapeutic clinical trials, due to the difficulty to measure the same phenomenon. In order to implement US in the management of patients with established or suspected gout the &quot;gout subgroup of the OMERACT US Working Group&quot; initiated a validation process. The first step was to obtain consensus-based definitions for the US elementary lesion as indicated by the literature review. This was accomplished by performing a Delphi exercise 14 . Thirty-five rheumatologists performing US and with an interest in gout were invited to participate, and 32 responded positively. After 3 Delphi rounds, &gt; 80% agreement was obtained for each definition Agreement was obtained to use the existing definitions for both synovitis and tenosynovitis 15 because these may be co-components in gout disease. Agreement could not be obtained to include synovitis (including Doppler activity) as an elementary lesion indicative of gout, because the presence of synovitis alone was not considered specific enough to define gout disease because it is a key component in other inflammatory arthropathies as well 14 . On the other hand, even if erosions may also be seen in other arthropathy conditions, since they may also be found extraarticularly in gout and may possibly have a slightly different appearance, it was decided to test, as part of the Delphi exercise, whether the existing definition worked also in gout. Perfect agreement was obtained to keep the definition close to the definition used for erosions in general. The second step was to test the reliability of the obtained definitions in a Web exercise consisting of static images of the elementary lesions. The Web exercise included 110 US images of the 4 lesions obtained from feet and knees and 20 of these images were shown twice in order to test both interand intrareader reliability. Twenty-seven of the 35 rheumatologists participating in the Delphi exercise participated in the reliability study. Cohen&apos;s κ was used to evaluate interand intrareader reliability. Κ values 0-0.20 were considered poor; 0.20-0.40 fair; 0.40-0.60 moderate; 0.60-0.80 good; and 0.80-1 excellent The third step was to test the agreement and reliability of the elementary lesions in a cohort of patients with gout. Sixteen of the rheumatologists previously involved in the first and second step participated in a workshop with 8 patients with crystal-proven gout. Both intra-and inter-reader reliability was assessed by scanning the patients twice within the same day. The areas of attention were the intercondylar region of the knee, the 1st metatarsophalangeal (MTP) joint, and the patellar tendon. Cohen&apos;s κ was used to evaluate inter-and intrareader reliability. Κ values of 0-0.20 were considered poor; 0.20-0.40 fair; 0.40-0.60 moderate; 0.60-0.80 good; and 0.80-1 excellen

Users' perspectives of barriers and facilitators to implementing EHR in Canada: A study protocol

<p>Abstract</p> <p>Background</p> <p>In Canada, federal, provincial, and territorial governments are developing an ambitious project to implement an interoperable electronic health record (EHR). Benefits for patients, healthcare professionals, organizations, and the public in general are expected. However, adoption of an interoperable EHR remains an important issue because many previous EHR projects have failed due to the lack of integration into practices and organizations. Furthermore, perceptions of the EHR vary between end-user groups, adding to the complexity of implementing this technology. Our aim is to produce a comprehensive synthesis of actual knowledge on the barriers and facilitators influencing the adoption of an interoperable EHR among its various users and beneficiaries.</p> <p>Methods</p> <p>First, we will conduct a comprehensive review of the scientific literature and other published documentation on the barriers and facilitators to the implementation of the EHR. Standardized literature search and data extraction methods will be used. Studies' quality and relevance to inform decisions on EHR implementation will be assessed. For each group of EHR users identified, barriers and facilitators will be categorized and compiled using narrative synthesis and meta-analytical techniques. The principal factors identified for each group of EHR users will then be validated for its applicability to various Canadian contexts through a two-round Delphi study, involving representatives from each end-user groups. Continuous exchanges with decision makers and periodic knowledge transfer activities are planned to facilitate the dissemination and utilization of research results in policies regarding the implementation of EHR in the Canadian healthcare system.</p> <p>Discussion</p> <p>Given the imminence of an interoperable EHR in Canada, knowledge and evidence are urgently needed to prepare this major shift in our healthcare system and to oversee the factors that could affect its adoption and integration by all its potential users. This synthesis will be the first to systematically summarize the barriers and facilitators to EHR adoption perceived by different groups and to consider the local contexts in order to ensure the applicability of this knowledge to the particular realities of various Canadian jurisdictions. This comprehensive and rigorous strategy could be replicated in other settings.</p

Population genomics of speciation and admixture

The application of population genomics to the understanding of speciation has led to the emerging field of speciation genomics. This has brought new insight into how divergence builds up within the genome during speciation and is also revealing the extent to which species can continue to exchange genetic material despite reproductive barriers. It is also providing powerful new approaches for linking genotype to phenotype in admixed populations. In this chapter, we give an overview of some of the methods that have been used and some of the novel insights gained. We also outline some of the pitfalls of the most commonly used methods and possible problems with interpretation of the results

Mutant Versions of the S. cerevisiae Transcription Elongation Factor Spt16 Define Regions of Spt16 That Functionally Interact with Histone H3

In eukaryotic cells, the highly conserved FACT (FAcilitates Chromatin Transcription) complex plays important roles in several chromatin-based processes including transcription initiation and elongation. During transcription elongation, the FACT complex interacts directly with nucleosomes to facilitate histone removal upon RNA polymerase II (Pol II) passage and assists in the reconstitution of nucleosomes following Pol II passage. Although the contribution of the FACT complex to the process of transcription elongation has been well established, the mechanisms that govern interactions between FACT and chromatin still remain to be fully elucidated. Using the budding yeast Saccharomyces cerevisiae as a model system, we provide evidence that the middle domain of the FACT subunit Spt16 – the Spt16-M domain – is involved in functional interactions with histone H3. Our results show that the Spt16-M domain plays a role in the prevention of cryptic intragenic transcription during transcription elongation and also suggest that the Spt16-M domain has a function in regulating dissociation of Spt16 from chromatin at the end of the transcription process. We also provide evidence for a role for the extreme carboxy terminus of Spt16 in functional interactions with histone H3. Taken together, our studies point to previously undescribed roles for the Spt16 M-domain and extreme carboxy terminus in regulating interactions between Spt16 and chromatin during the process of transcription elongation