Activity pattern, or the time of day when an animal is awake and active, is highly associated with that animal's ecology. There are two principal activity patterns: diurnal, or awake during the day ...in a photopic, or high light level, environment; and nocturnal, awake at night in scotopic, or low light level, conditions. Nocturnal and diurnal birds exhibit characteristic eye shapes associated with their activity pattern, with nocturnal bird eyes optimized for visual sensitivity with large corneal diameters relative to their eye axial lengths, and diurnal birds optimized for visual acuity, with larger axial lengths of the eye relative to their corneal diameters. The current study had three aims: (1) to quantify the nature of the relationship between the avian eye and its associated bony anatomy, the orbit and the sclerotic ring; (2) to investigate how activity pattern is reflected in that bony anatomy; and (3) to identify how much bony anatomy is required to interpret activity pattern reliably for a bird that does not have the soft tissue available for study, specifically, for a fossil. Knowledge of extinct avian activity patterns would be useful in making palaeoecological interpretations. Here eye, orbit and sclerotic ring morphologies of 140 nocturnal and diurnal bird species are analysed in a phylogenetic context. Although there is a close relationship between the avian eye and orbit, activity pattern can only be reliably interpreted for bony‐only specimens, such as a fossil, that include both measurements of the sclerotic ring and orbit depth. Any missing data render the fossil analysis inaccurate, including fossil specimens that are flat and therefore do not have an orbit depth available. For example, activity pattern cannot be determined with confidence for Archaeopteryx lithographica, which has a complete sclerotic ring but no orbit depth measurement. Many of the bird fossils currently available that retain a good sclerotic ring tend to be flat specimens, while three‐dimensionally preserved bird fossils tend not to have a well‐preserved sclerotic ring or a well‐defined optic foramen, necessary for delimiting the orbit depth.
Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant genetic disorder of aberrant blood vessel development characterised by arteriovenous malformations. HHT is associated with ...significant morbidity due to complications including epistaxis, gastrointestinal bleeding and stroke. We explored the hypothesis that a diagnosis of HHT is associated with sex, socioeconomic status and geographical location.
We used The Health Improvement Network, a longitudinal, computerised general practice database covering 5% of the UK population to calculate prevalence estimates for HHT stratified by age, sex, socioeconomic status and geographical location.
The 2010 UK point prevalence for HHT was 1.06/10 000 person years (95% CI 0.95 to 1.17) or 1 in 9400 individuals. The diagnosed prevalence of HHT was significantly higher in women compared with men (adjusted prevalence rate ratio (PRR) 1.53, 95% CI 1.24 to 1.88) and in those from the most affluent socioeconomic group compared with the least (adjusted PRR 1.74, 95% CI 1.14 to 2.64). The PRR varied between different regions of the UK, being highest in the South West and lowest in the West Midlands (adjusted PRR for former compared with latter 1.86, 95% CI 1.61 to 2.15).
HHT prevalence is more common in the UK population than previously demonstrated, though this updated figure is still likely to be an underestimate. HHT appears to be significantly under-diagnosed in men, which is likely to reflect their lower rates of consultation with primary care services. There is under-diagnosis in patients from lower socioeconomic groups and a marked variation in the prevalence of diagnosis between different geographical regions across the UK that requires further investigation.
Hypothermic machine perfusion (HMP) is increasingly used in deceased donor kidney transplantation, but controversy exists regarding the value of perfusion biomarkers and pump parameters for assessing ...organ quality. We prospectively determined associations between perfusate biomarkers (neutrophil gelatinase–associated lipocalin NGAL, kidney injury molecule 1, IL‐18 and liver‐type fatty acid–binding protein L‐FABP) and pump parameters (resistance and flow) with outcomes of delayed graft function (DGF) and 6‐mo estimated GFR (eGFR). DGF occurred in 230 of 671 (34%) recipients. Only 1‐h flow was inversely associated with DGF. Higher NGAL or L‐FABP concentrations and increased resistance were inversely associated with 6‐mo eGFR, whereas higher flow was associated with higher adjusted 6‐mo eGFR. Discarded kidneys had consistently higher median resistance and lower median flow than transplanted kidneys, but median perfusate biomarker concentrations were either lower or not significantly different in discarded compared with transplanted kidneys. Notably, most recipients of transplanted kidneys with isolated “undesirable” biomarker levels or HMP parameters experienced acceptable 6‐mo allograft function, suggesting these characteristics should not be used in isolation for discard decisions. Additional studies must confirm the utility of combining HMP measurements with other characteristics to assess kidney quality.
This prospective cohort study of deceased donor kidney transplant recipients whose allografts underwent hypothermic machine perfusion finds an association of the greater perfusate flow on pump with lower rates of delayed graft function, while greater perfusate flow and lower concentrations of perfusate NGAL and L‐FABP measured at the end of pumping are associated with better allograft function by 6 months after transplantation.
To cite this article: Beghé B, Hall IP, Parker SG, Moffatt MF, Wardlaw A, Connolly MJ, Fabbri LM, Ruse C, Sayers I. Polymorphisms in IL13 pathway genes in asthma and chronic obstructive pulmonary ...disease. Allergy 2010; 65: 474-481. Asthma and chronic obstructive pulmonary disease (COPD) are chronic respiratory diseases involving an interaction between genetic and environmental factors. Interleukin-13 (IL13) has been suggested to have a role in both asthma and COPD. We investigated whether single nucleotide polymorphisms (SNPs) in the IL13 pathway may contribute to the susceptibility and severity of asthma and COPD in adults. Twelve SNPs in IL13 pathway genes -IL4, IL13, IL4RA, IL13RA1, IL13RA2 and STAT6- were genotyped in subjects with asthma (n = 299) and in subjects with COPD or healthy smokers (n = 992). Genetic association was evaluated using genotype and allele models for asthma severity, atopy phenotypes and COPD susceptibility. Linear regression was used to determine the effects of polymorphism on baseline lung function (FEV₁, FEV₁/FVC). In asthmatics, three IL13 SNPs - rs1881457(-1512), rs1800925(-1111) and rs20541(R130Q) - were associated with atopy risk. One SNP in IL4RA1 rs1805010(I75V) was associated with asthma severity, and several IL13 SNPs showed borderline significance. IL13 SNPs rs1881457(-1512) and rs1800925(-1111) were associated with better FEV₁ and FEV₁/FVC in asthmatics. IL13 SNPs rs2066960(intron 1), rs20541(R130Q) and rs1295685(exon 4) were associated with COPD risk and lower baseline lung function in the recessive model. In females, but not in males, rs2250747 of the IL13RA1 gene was associated with COPD and lower FEV₁. These data suggest that IL13 SNPs (promoter and coding region) and, to a lesser extent, IL4RA SNPs may contribute to atopy and asthma. We also provide tentative evidence that IL13 SNPs in the coding region may be of significance in COPD susceptibility.
Background: Rheumatoid arthritis (RA) is associated with increased cardiovascular mortality for reasons which are insufficiently understood. Chronic inflammation may impair vascular function and lead ...to an increase of arterial stiffness, an important determinant of cardiovascular risk. Objective: To investigate the augmentation index (AIx) as a measure of arterial stiffness in patients with RA, free of cardiovascular disease or risk factors, by means of a matched cohort pilot study. Method: Patients with a diagnosis of RA, aged 50 years or younger, were screened for the absence of clinical cardiovascular disease and risk factors, such as smoking, hypercholesterolaemia, hypertension, and excessive systemic steroid use. Suitable subjects were assessed by non-invasive radial pulse wave analysis to determine their AIx. These data were compared with those from healthy controls, matched closely for sex, age, mean peripheral blood pressure, heart rate, and height. Results: 14 suitable patients (11 female; mean (SD) age 42 (6) years, mean RA duration 11 (6) years; mean C reactive protein 19 (15) mg/l, no clinical systemic rheumatoid vasculitis) and matched controls were identified. The RA group had a higher mean (SD) AIx and mean (SD) central blood pressure (BP) than the control group: AIx 26.2 (6.7) v 18.9 (10.8)%, p=0.028; mean central BP 91.3 (7.8) v 88.2 (8.9) mm Hg, p<0.0001, by two tailed, paired t test. Conclusions: This preliminary study suggests that RA is associated with increased arterial stiffness and central BP, independently of clinically manifest cardiovascular disease or risk factors. This may contribute to the increased cardiovascular mortality in RA.
A decadal resolution time series of sea surface temperature (SST) spanning the last two millennia is reconstructed by combining a proxy record from a new sediment sequence with previously published ...data from core MD99–2275, north of Iceland. The alkenone based SST reconstruction is validated with historic observational data and compared to a new similar temporal resolution reconstruction obtained from sediment core RAPiD21–3K, in the subpolar North Atlantic. The two SST paleorecords show consistent multidecadal scale coolings throughout the interval and similar expressions during the contrasted climatic periods ‘colloquially known’ as the Medieval Climatic Anomaly (MCA) and Little Ice Age (LIA). In order to further understand the temporal and spatial SST variations and investigate the influence of natural forcings on the observed SST changes during the last millennium, we compare our time series to simulations using the Institut Pierre‐Simon Laplace IPSLCM4‐v2 climate model. This comparison highlights the potential importance of volcanism as a natural forcing driving coherent abrupt cooling events captured in the subpolar North Atlantic records.
Key Points
Comparative analysis of marine paleo proxy data to simulation of the last 1000 years
The impact of volcanism on ocean variability
The ongoing worldwide spread of the H5N1 influenza virus in birds has increased concerns of a new human influenza pandemic and a number of surveillance initiatives are planned, or are in place, to ...monitor the impact of a pandemic in near real-time. Using epidemiological data collected during the early stages of an outbreak, we show how the timing of the maximum prevalence of the pandemic wave, along with its amplitude and duration, might be predicted by fitting a mass-action epidemic model to the surveillance data by standard regression analysis. This method is validated by applying the model to routine data collected in the United Kingdom during the different waves of the previous three pandemics. The success of the method in forecasting historical prevalence suggests that such outbreaks conform reasonably well to the theoretical model, a factor which may be exploited in a future pandemic to update ongoing planning and response.
Context-dependent plasticity in auditory processing is achieved in part by physiological mechanisms that link behavioral state to neural responses to sound. The neuromodulator serotonin has many ...characteristics suitable for such a role. Serotonergic neurons are extrinsic to the auditory system but send projections to most auditory regions. These projections release serotonin during particular behavioral contexts. Heightened levels of behavioral arousal and specific extrinsic events, including stressful or social events, increase serotonin availability in the auditory system. Although the release of serotonin is likely to be relatively diffuse, highly specific effects of serotonin on auditory neural circuitry are achieved through the localization of serotonergic projections, and through a large array of receptor types that are expressed by specific subsets of auditory neurons. Through this array, serotonin enacts plasticity in auditory processing in multiple ways. Serotonin changes the responses of auditory neurons to input through the alteration of intrinsic and synaptic properties, and alters both short- and long-term forms of plasticity. The infrastructure of the serotonergic system itself is also plastic, responding to age and cochlear trauma. These diverse findings support a view of serotonin as a widespread mechanism for behaviorally relevant plasticity in the regulation of auditory processing. This view also accommodates models of how the same regulatory mechanism can have pathological consequences for auditory processing.
► Serotonin is a context-dependent neuromodulator of auditory processing. ► Serotonergic projections are found throughout the auditory system. ► Auditory serotonin rises during behavioral arousal and specific events. ► Serotonin influences pre- and postsynaptic response properties. ► The serotonergic infrastructure is itself subject to plasticity.
Recent meta-analyses of genome-wide association studies have identified single nucleotide polymorphisms (SNPs) within/near 54 genes associated with lung function measures. Current understanding of ...the contribution of these genes to human lung development is limited. We set out to further define i) the expression profile of these genes during human lung development using a unique set of resources to examine both mRNA and protein expression and ii) the link between key polymorphisms and genes using expression quantitative trait loci (eQTL) approaches.
The mRNA expression profile of lung function associated genes across pseudoglandular and canalicular stages of lung development were determined using expression array data of 38 human fetal lungs. eQTLs were investigated for selected genes using blood cell and lung tissue data. Immunohistochemistry of the top 5 candidates was performed in a panel of 24 fetal lung samples.
Twenty-nine lung function associated genes were differentially expressed during lung development at the mRNA level. The greatest magnitude of effect was observed for 5 genes; TMEM163, FAM13A and HHIP which had increasing expression and CDC123 and PTCH1 with decreased expression across developmental stages. Focussed eQTL analyses investigating SNPs in these five loci identified several cis-eQTL's. Protein expression of TMEM163 increased and CDC123 decreased with fetal lung age in agreement with mRNA data. Protein expression in FAM13A, HHIP and PTCH1 remained relatively constant throughout lung development.
We have identified that > 50 % of lung function associated genes show evidence of differential expression during lung development and we show that in particular TMEM163 and CDC123 are differentially expressed at both the mRNA and protein levels. Our data provides a systematic evaluation of lung function associated genes in this context and offers some insight into the potential role of several of these genes in contributing to human lung development.
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