Feather development genes and associated regulatory innovation predate the origin of Dinosauria

The evolution of avian feathers have recently been illuminated by fossils and the identification of genes involved in feather patterning and morphogenesis. However, molecular studies have focused mainly on protein-coding genes. Using comparative genomics and more than 600,000 conserved regulatory elements, we show that patterns of genome evolution in the vicinity of feather genes are consistent with a major role for regulatory innovation in the evolution of feathers. Rates of innovation at feather regulatory elements exhibit an extended period of innovation with peaks in the ancestors of amniotes and archosaurs. We estimate that 86% of such regulatory elements were present prior to the origin of Dinosauria. On the branch leading to modern birds, we detect a strong signal of regulatory innovation near IGFBP2 and IGFBP5, which have roles in body size reduction, and may represent a genomic signature for the miniaturization of dinosaurian body size preceding the origin of flight.Organismic and Evolutionary Biolog

Comparative Genomics Search for Losses of Long-Established Genes on the Human Lineage

Taking advantage of the complete genome sequences of several mammals, we developed a novel method to detect losses of well-established genes in the human genome through syntenic mapping of gene structures between the human, mouse, and dog genomes. Unlike most previous genomic methods for pseudogene identification, this analysis is able to differentiate losses of well-established genes from pseudogenes formed shortly after segmental duplication or generated via retrotransposition. Therefore, it enables us to find genes that were inactivated long after their birth, which were likely to have evolved nonredundant biological functions before being inactivated. The method was used to look for gene losses along the human lineage during the approximately 75 million years (My) since the common ancestor of primates and rodents (the euarchontoglire crown group). We identified 26 losses of well-established genes in the human genome that were all lost at least 50 My after their birth. Many of them were previously characterized pseudogenes in the human genome, such as GULO and UOX. Our methodology is highly effective at identifying losses of single-copy genes of ancient origin, allowing us to find a few well-known pseudogenes in the human genome missed by previous high-throughput genome-wide studies. In addition to confirming previously known gene losses, we identified 16 previously uncharacterized human pseudogenes that are definitive losses of long-established genes. Among them is ACYL3, an ancient enzyme present in archaea, bacteria, and eukaryotes, but lost approximately 6 to 8 Mya in the ancestor of humans and chimps. Although losses of well-established genes do not equate to adaptive gene losses, they are a useful proxy to use when searching for such genetic changes. This is especially true for adaptive losses that occurred more than 250,000 years ago, since any genetic evidence of the selective sweep indicative of such an event has been erased

A structured framework for improving outbreak investigation audits

Outbreak investigation is a core function of public health agencies. Suboptimal outbreak investigation endangers both public health and agency reputations. While audits of clinical medical and nursing practice are conducted as part of continuous quality improvement, public health agencies rarely make systematic use of structured audits to ensure best practice for outbreak responses, and there is limited guidance or policy to guide outbreak audit. A framework for prioritising which outbreak investigations to audit, an approach for conducting a successful audit, and a template for audit trigger questions was developed and trialled in four foodborne outbreaks and a respiratory disease outbreak in Australia. The following issues were identified across several structured audits: the need for clear definitions of roles and responsibilities both within and between agencies, improved communication between agencies and with external stakeholders involved in outbreaks, and the need for development of performance standards in outbreak investigations - particularly in relation to timeliness of response. Participants considered the audit process and methodology to be clear, useful, and non-threatening. Most audits can be conducted within two to three hours, however, some participants felt this limited the scope of the audit. The framework was acceptable to participants, provided an opportunity for clarifying perceptions and enhancing partnership approaches, and provided useful recommendations for approaching future outbreaks. Future challenges include incorporating feedback from broader stakeholder groups, for example those of affected cases, institutions and businesses; assessing the quality of a specific audit; developing training for both participants and facilitators; and building a central capacity to support jurisdictions embarking on an audit. The incorporation of measurable performance criteria or sharing of benchmark performance criteria will assist in the standardisation of outbreak investigation audit and further quality improvement

Quantification of atopy, lung function and airway hypersensitivity in adults

<p>Abstract</p> <p>Background</p> <p>Studies in children have shown that concentration of specific serum IgE (sIgE) and size of skin tests to inhalant allergens better predict wheezing and reduced lung function than the information on presence or absence of atopy. However, very few studies in adults have investigated the relationship of quantitative atopy with lung function and airway hyperresponsiveness (AHR).</p> <p>Objective</p> <p>To determine the association between lung function and AHR and quantitative atopy in a large sample of adults from the UK.</p> <p>Methods</p> <p>FEV₁ and FVC (% predicted) were measured using spirometry and airway responsiveness by methacholine challenge (5-breath dosimeter protocol) in 983 subjects (random sample of 800 parents of children enrolled in a population-based birth cohort enriched with 183 patients with physician-diagnosed asthma). Atopic status was assessed by skin prick tests (SPT) and measurement of sIgE (common inhalant allergens). We also measured indoor allergen exposure in subjects' homes.</p> <p>Results</p> <p>Spirometry was completed by 792 subjects and 626 underwent methacholine challenge, with 100 (16.0%) having AHR (dose-response slope>25). Using sIgE as a continuous variable in a multiple linear regression analysis, we found that increasing levels of sIgE to mite, cat and dog were significantly associated with lower FEV₁ (mite p = 0.001, cat p = 0.0001, dog p = 2.95 × 10^-8). Similar findings were observed when using the size of wheal on skin testing as a continuous variable, with significantly poorer lung function with increasing skin test size (mite p = 8.23 × 10^-8, cat p = 3.93 × 10^-10, dog p = 3.03 × 10^-15, grass p = 2.95 × 10^-9). The association between quantitative atopy with lung function and AHR remained unchanged when we repeated the analyses amongst subjects defined as sensitised using standard definitions (sIgE>0.35 kUa/l, SPT-3 mm>negative control).</p> <p>Conclusions</p> <p>In the studied population, lung function decreased and AHR increased with increasing sIgE levels or SPT wheal diameter to inhalant allergens, suggesting that atopy may not be a dichotomous outcome influencing lung function and AHR.</p

CLEC-2 and Syk in the megakaryocytic/platelet lineage are essential for development

The C-type lectin receptor CLEC-2 signals through a pathway that is critically dependent on the tyrosine kinase Syk. We show that homozygous loss of either protein results in defects in brain vascular and lymphatic development, lung inflation and perinatal lethality. Furthermore, we find that conditional deletion of Syk in the haematopoietic lineage, or conditional deletion of CLEC-2 or Syk in the megakaryocyte/platelet lineage, also causes defects in brain vascular and lymphatic development, although the mice are viable. In contrast, conditional deletion of Syk in other haematopoietic lineages had no effect on viability or brain vasculature and lymphatic development. We show that platelets, but not platelet releasate, modulate the migration and intercellular adhesion of lymphatic endothelial cells through a pathway that is dependent on CLEC-2 and Syk. These studies demonstrate that megakaryocyte/platelet expression of CLEC-2 and Syk is required for normal brain vasculature and lymphatic development and that platelet CLEC-2 and Syk directly modulate lymphatic endothelial cell behaviour in vitro

Endangered Species Hold Clues to Human Evolution

We report that 18 conserved, and by extension functional, elements in the human genome are the result of retroposon insertions that are evolving under purifying selection in mammals. We show evidence that 1 of the 18 elements regulates the expression of ASXL3 during development by encoding an alternatively spliced exon that causes nonsense-mediated decay of the transcript. The retroposon that gave rise to these functional elements was quickly inactivated in the mammalian ancestor, and all traces of it have been lost due to neutral decay. However, the tuatara has maintained a near-ancestral version of this retroposon in its extant genome, which allows us to connect the 18 human elements to the evolutionary events that created them. We propose that conservation efforts over more than 100 years may not have only prevented the tuatara from going extinct but could have preserved our ability to understand the evolutionary history of functional elements in the human genome. Through simulations, we argue that species with historically low population sizes are more likely to harbor ancient mobile elements for long periods of time and in near-ancestral states, making these species indispensable in understanding the evolutionary origin of functional elements in the human genome

The relationship of the factor V Leiden mutation or the deletion-deletion polymorphism of the angiotensin converting enzyme to postoperative thromboembolic events following total joint arthroplasty

BACKGROUND: Although all patients undergoing total joint arthroplasty are subjected to similar risk factors that predispose to thromboembolism, only a subset of patients develop this complication. The objective of this study was to determine whether a specific genetic profile is associated with a higher risk of developing a postoperative thromboembolic complication. Specifically, we examined if the Factor V Leiden (FVL) mutation or the deletion polymorphism of the angiotensin-converting enzyme (ACE) gene increased a patient's risk for postoperative thromboembolic events. The FVL mutation has been associated with an increased risk of idiopathic thromboembolism and the deletion polymorphism of the ACE gene has been associated with increased vascular tone, attenuated fibrinolysis and increased platelet aggregation. METHODS: The presence of these genetic profiles was determined for 38 patients who had a postoperative symptomatic pulmonary embolus or proximal deep venous thrombosis and 241 control patients without thrombosis using molecular biological techniques. RESULTS: The Factor V Leiden mutation was present in none of the 38 experimental patients and in 3% or 8 of the 241 controls (p = 0.26). Similarly there was no difference detected in the distribution of polymorphisms for the ACE gene with the deletion-deletion genotype present in 36% or 13 of the 38 experimental patients and in 31% or 74 of the 241 controls (p = 0.32). CONCLUSIONS: Our results suggest that neither of these potentially hypercoaguable states are associated with an increased risk of symptomatic thromboembolic events following total hip or knee arthroplasty in patients receiving pharmacological thromboprophylaxis

The genome of the green anole lizard and a comparative analysis with birds and mammals

The evolution of the amniotic egg was one of the great evolutionary innovations in the history of life, freeing vertebrates from an obligatory connection to water and thus permitting the conquest of terrestrial environments1. Among amniotes, genome sequences are available for mammals2 and birds3–5, but not for non-avian reptiles. Here we report the genome sequence of the North American green anole lizard, Anolis carolinensis. We find that A. carolinensis microchromosomes are highly syntenic with chicken microchromosomes, yet do not exhibit the high GC and low repeat content that are characteristic of avian microchromosomes3. Also, A. carolinensis mobile elements are very young and diverse – more so than in any other sequenced amniote genome. This lizard genome’s GC content is also unusual in its homogeneity, unlike the regionally variable GC content found in mammals and birds6. We describe and assign sequence to the previously unknown A. carolinensis X chromosome. Comparative gene analysis shows that amniote egg proteins have evolved significantly more rapidly than other proteins. An anole phylogeny resolves basal branches to illuminate the history of their repeated adaptive radiations

Osteoarthritis and functional disability: results of a cross sectional study among primary care patients in Germany

Contains fulltext : 52359.pdf ( ) (Open Access)BACKGROUND: The aim of the study was to determine factors associated with functional disability in patients with OA. METHODS: 1250 questionnaires were distributed to OA outpatients from 75 general practices; 1021 (81.6%) were returned. Questionnaires included sociodemographic data, the short form of the Arthritis Impact Measurement Scale (AIMS2-SF), and the Patient Health Questionnaire (PHQ-9) to assess concomitant depression. A hierarchical stepwise multiple regression analysis with the AIMS2-SF dimension "lower body" as dependent was performed. RESULTS: Main factors associated with functional disability were depression symptoms, as reflected in a high score of the PHQ-9 (beta = 0.446; p < 0.0009), pain as reflected in the AIMS2-SF symptom scale (beta = 0.412; p = 0.001), and few social contacts (beta = 0.201; p < 0.042). A high body mass index was associated with lower functional ability (beta = 0.332; p = 0.005) whereas a higher educational level (beta = -0.279; p = 0.029) predicted less impairment. Increased age was a weak predictor (beta = 0.178; p = 0.001) of disability. With a p of 0.062 the radiological severity according to the grading of Kellgren and Lawrence slightly surpassed the required significance level for remaining in the final regression model. CONCLUSION: The results emphasize that psychological as well as physical factors need to be addressed similarly to improve functional ability of patients suffering from OA. More research with multifaceted and tailored interventions is needed to determine how these factors can be targeted appropriately

Fish and fishing in the Roman world

This article focuses on two aspects related to fish and fishing. It first discusses the social context for the consumption of preserved and fresh fish, showing that generally consumption of certain types of fresh fish conferred status, whereas consumption of preserved fish, being more affordable, was attested across social strata. The paper then moves on to examine the organization of the ‘fishing industry’, specifically the relationship between fish-salting establishments and the fishermen who provided the fish. Although we have many literary, documentary, and archaeological sources for fish preservation and fishing techniques in classical antiquity, the fishermen engaged in large-scale fishing remain rather elusive