The causes and consequences of inter-individual variation in corticosterone in the blue tit, Cyanistes caeruleus

Corticosterone (CORT), the main glucocorticoid in birds, plays a fundamental role in maintaining homeostasis and energy-balance, and is therefore tightly linked to an individual’s energetic state and the prevalent environmental conditions. CORT also has pleiotropic effects, ranging from reproductive function, the regulation of behaviour, morphology and immune function. Thus, inter-individual variation in CORT can potentially underpin a range of life-history traits, and through its pleiotropic effects act as a physiological mediator of reproductive decisions, causing birds to direct resources towards reproduction or self-maintenance dependent upon energetic condition and/or environmental quality. In turn, the role of CORT as a mediator of life-history traits has lead to the suggestion that inter-individual variation in CORT may be associated with individual differences in fitness. Despite this, the causes and consequences of large inter-individual variation in baseline CORT, specifically during reproduction, remain relatively unknown. The main aim of this thesis was to address these knowledge gaps by monitoring a nest-box population of blue tits, Cyanistes caeruleus, breeding on the east banks of Loch Lomond, UK over three years (2008-2010), and measuring baseline CORT concentrations in both adult and nestling birds at a standard stage of breeding in each year. Although environmental quality is often linked to variation in baseline CORT in breeding birds, this has rarely been investigated at the individual level. Chapter 2 focuses on the relationship between foraging conditions measured at the territory-scale and baseline CORT in adult and nestlings in 2008-2010. Synchrony with the peak in caterpillar abundance was the only factor to influence nestling CORT, and only in 2008. However, I found that synchrony between breeding and the peak in caterpillar abundance, weather variables and the density of oak trees influenced baseline CORT in adult birds. Importantly, the relationships between adult baseline CORT and these foraging conditions were only evident in some years; when conditions were most demanding. In addition, the effects of the foraging conditions measured upon adult baseline CORT appear to be synergetic and/or additive in nature. As inclement environmental conditions are often associated with elevated baseline CORT and reduced fitness in birds, it has been suggested that elevated baseline CORT should also be associated with reduced fitness (the ‘CORT-Fitness’ Hypothesis). However, this may not be the case, as modulation of CORT in the face of environmental challenges can adaptively influence physiology and behaviour to improve breeding performance and/or survival. In Chapter 3, I tested these assumptions and my results indicate that the foraging conditions linked to maternal baseline CORT differ to those associated with a proxy of fitness i.e. reproductive success. Specifically, maternal baseline CORT appears to be linked with factors that affect energetic demand, i.e. movement between trees, rather than reproductive success, i.e. total number of prey provided to offspring. In addition, in 2009 only, maternal baseline CORT was positively correlated with fledging number. In Chapter 4, I investigate whether there is a link between maternal baseline CORT and brood sex ratio adjustment over three years. I discovered that maternal baseline CORT was not correlated with brood sex ratio in any year. Maternal body condition, however, was linked to brood sex ratio adjustment in one year. Furthermore, experimental manipulation of maternal CORT during egg laying did not result in brood sex ratio adjustment or affect maternal condition, hatching success or chick development. Chapter 5 investigates the role of maternal baseline CORT in reproductive trade-offs. I reduced the costs of egg laying through supplemental feeding and compared maternal baseline CORT, brood care and maternal return rates between manipulated and control mothers. Reducing costs negated the physiological stress associated with provisioning effort in manipulated mothers and improved their return rates the following year compared with controls. Therefore, maternal CORT may mediate reproductive trade-offs in this species. As baseline CORT is often linked with energetic status and environmental conditions, and there is some evidence that CORT affects feather growth, I hypothesised that it may be linked to the expression of UV colouration in the crown feathers of female birds (Chapter 6). The results show that baseline CORT was indeed negatively correlated with UV colouration, and that UV colouration was positively correlated with reproductive success consistently over the three years, thus suggesting this trait signals maternal quality. Finally, Chapter 7 summarizes the main findings and considers how my results add to our knowledge base and discusses pertinent avenues of future research. This thesis presents compelling evidence that inter-individual variation in baseline CORT is significant, as the results show that it is associated with foraging conditions, reproductive success and may also influence reproductive trade-offs and UV plumage colouration. However, the results do not support a role for baseline CORT in brood sex ratio adjustments in blue tits. The results also reveal the complexity of the relationships between inter-individual variation in baseline CORT, environmental conditions and reproductive success. Specifically, both foraging conditions and proxies of fitness, i.e. reproductive success were linked to baseline CORT differently between years, most likely due to the contrasting conditions experienced in those years. Therefore, although inter-individual variation in CORT is linked to life-history traits in breeding birds, relating this variation to individual fitness is challenging. Furthermore, there remains a lack of knowledge concerning the repeatability of baseline CORT concentrations in blue tits. Ultimately, my thesis suggests that in order to achieve a full understanding of how inter-individual variation in baseline CORT is linked to fitness, single year or short-term studies are inadequate; instead, researchers must relate individual differences to long-term measures of fitness

Perch, Perca fluviatilis show a directional preference for, but do not increase attacks toward, prey in response to water-borne cortisol

In freshwater environments, chemosensory cues play an important role in predatorprey interactions. Prey use a variety of chemosensory cues to detect and avoid predators. However, whether predators use the chemical cues released by disturbed or stressed prey has received less attention. Here we tested the hypothesis that the disturbance cue cortisol, in conjunction with visual cues of prey, elevates predatory behavior. We presented predators (perch, Perca fluviatilis) with three chemosensory choice tests and recorded their location, orientation, and aggressive behavior. We compared the responses of predators when provided with (i) visual cues of prey only (two adjacent tanks containing sticklebacks); (ii) visual and natural chemical cues of prey vs. visual cues only; and (iii) visual cues of prey with cortisol vs. visual cues only. Perch spent a significantly higher proportion of time in proximity to prey, and orientated toward prey more, when presented with a cortisol stimulus plus visual cues, relative to presentations of visual and natural chemical cues of prey, or visual cues of prey only. There was a trend that perch directed a higher proportion of predatory behaviors (number of lunges) toward sticklebacks when presented with a cortisol stimulus plus visual cues, relative to the other chemosensory conditions. But they did not show a significant increase in total predatory behavior in response to cortisol. Therefore, it is not clear whether water-borne cortisol, in conjunction with visual cues of prey, affects predatory behavior. Our results provide evidence that cortisol could be a source of public information about prey state and/or disturbance, but further work is required to confirm this

Continuous wave optical parametric oscillator for quartz-enhanced photoacoustic trace gas sensing

A continuous wave optical parametric oscillator, generating up to 300 mW idler output in the 3–4 μm wavelength region, and pumped by a fiber-amplified DBR diode laser is used for trace gas detection by means of quartz-enhanced photoacoustic spectroscopy (QEPAS). Mode-hop-free tuning of the OPO output over 5.2 cm-1 and continuous spectral coverage exceeding 16.5 cm-1 were achieved via electronic pump source tuning alone. Online monitoring of the idler wavelength, with feedback to the DBR diode laser, provided an automated closed-loop control allowing arbitrary idler wavelength selection within the pump tuning range and locking of the idler wavelength with a stability of 1.7×10-3 cm-1 over at least 30 min.\ud \ud Using this approach, we locked the idler wavelength at an ethane absorption peak and obtained QEPAS data to verify the linear response of the QEPAS signal at different ethane concentrations (100 ppbv-20 ppmv) and different power levels. The detection limit for ethane was determined to be 13 ppbv (20 s averaging), corresponding to a normalized noise equivalent absorption coefficient of 4.4×10-7 cm-1  W/Hz1/2

Digital Silicon Photomultipliers with OR/XOR Pulse Combining Techniques

A recently proposed XOR-based digital silicon photomultiplier (dSiPM) is compared against the OR-based counterpart. We show experimental data from a set of single-photon avalanche diode (SPAD) pixel arrays in 130-nm CMOS process with selectable OR tree and XOR tree for direct comparison. We demonstrate how XOR-based dSiPMs solve the limitation caused by monostable circuits and reach higher maximum count rates compared with optimized OR-based dSiPMs. The increased throughput of the SPAD array allows higher sampling rates for the digitization of the light signal enhancing dynamic range and linearity

Nonsteroidal anti-inflammatory drug use and Alzheimer's disease risk: the MIRAGE Study

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAID) use may protect against Alzheimer's disease (AD) risk. We sought examine the association between NSAID use and risk of AD, and potential effect modification by APOE-ε4 carrier status and ethnicity. METHODS: The MIRAGE Study is a multi-center family study of genetic and environmental risk factors for AD. Subjects comprised 691 AD patients (probands) and 973 family members enrolled at 15 research centers between 1996 and 2002. The primary independent and dependent variables were prior NSAID use and AD case status, respectively. We stratified the dataset in order to evaluate whether the association between NSAID use and AD was similar in APOE-ε4 carriers and non-carriers. Ethnicity was similarly examined as an effect modifier. RESULTS: NSAID use was less frequent in cases compared to controls in the overall sample (adjusted OR = 0.64; 95% CI = 0.38–1.05). The benefit of NSAID use appeared more pronounced among APOE-ε4 carriers (adjusted OR = 0.49; 95% CI = 0.24–0.98) compared to non-carriers, although this association was not statistically significant. The pattern of association was similar in Caucasian and African Americans. CONCLUSIONS: NSAID use is inversely associated with AD and may be modified by APOE genotype. Prospective studies and clinical trials of sufficient power to detect effect modification by APOE-ε4 carrier status are needed

Biallelic Loss-of-Function Variants in BICD1 Are Associated with Peripheral Neuropathy and Hearing Loss

Hearing loss and peripheral neuropathy are two clinical entities that are genetically and phenotypically heterogeneous and sometimes co-occurring. Using exome sequencing and targeted segregation analysis, we investigated the genetic etiology of peripheral neuropathy and hearing loss in a large Ashkenazi Jewish family. Moreover, we assessed the production of the candidate protein via western blotting of lysates from fibroblasts from an affected individual and an unaffected control. Pathogenic variants in known disease genes associated with hearing loss and peripheral neuropathy were excluded. A homozygous frameshift variant in the BICD1 gene, c.1683dup (p.(Arg562Thrfs*18)), was identified in the proband and segregated with hearing loss and peripheral neuropathy in the family. The BIDC1 RNA analysis from patient fibroblasts showed a modest reduction in gene transcripts compared to the controls. In contrast, protein could not be detected in fibroblasts from a homozygous c.1683dup individual, whereas BICD1 was detected in an unaffected individual. Our findings indicate that bi-allelic loss-of-function variants in BICD1 are associated with hearing loss and peripheral neuropathy. Definitive evidence that bi-allelic loss-of-function variants in BICD1 cause peripheral neuropathy and hearing loss will require the identification of other families and individuals with similar variants with the same phenotype

Analysis of Photon Detection Efficiency and Dynamic Range in SPAD based Visible Light Receivers

We investigate the photon detection efficiency (PDE) and the dynamic range for digital silicon photomultipliers (dSiPMs) over a selection of design parameters: dSiPM unit cell dead time, PDE, unit cell area and fill factor, number of cells, and total dSiPM active area. Two receiver scaling scenarios are con-sidered: varying the number of cells for 1) a fixed unit cell area or 2) a fixed total dSiPM area. Theoretical and simulated results are confirmed with experimental data from a selection of dSiPMs realised on a test chip in130-nm CMOS process

A novel source of arterial valve cell linked to bicuspid aortic valve without rephe in mice

Abnormalities of the arterial valve leaflets, predominantly bicuspid aortic valve, are the commonest congenital malformations. Although many studies have investigated the development of the arterial valves, it has been assumed that, as with the atrioventricular valves, endocardial to mesenchymal transition (EndMT) is the predominant mechanism. We show that arterial is distinctly different from atrioventricular valve formation. Whilst the four septal valve leaflets are dominated by NCC and EndMT-derived cells, the intercalated leaflets differentiate directly from Tnnt2-Cre+/Isl1+ progenitors in the outflow wall, via a Notch-Jag dependent mechanism. Further, when this novel group of progenitors are disrupted, development of the intercalated leaflets is disrupted, resulting in leaflet dysplasia and bicuspid valves without raphe, most commonly affecting the aortic valve. This study thus overturns the dogma that heart valves are formed principally by EndMT, identifies a new source of valve interstitial cells, and provides a novel mechanism for causation of bicuspid aortic valves without raphe.British Heart Foundation RG/12/15/29935 Lorriane Eley Rachel V Richardson Lindsay Murphy Bill Chaudhry Deborah J Henderson; British Heart Foundation PG/15/46/31589 Lorriane Eley Bill Chaudhry Deborah J Henderson; Ministerio de Ciencia, Innovacion y Universidades of Spain CB16/11/00399 (Ciber Cardiovascular) Donal MacGrogan Alejandro Salguero-Jimenez Jose Luis de La Pompa; Ministerio de Ciencia, Innovacion y Universidades of Spain SAF2016-78370-R Donal MacGrogan Alejandro Salguero-Jimenez Jose Luis de La Pompa; Ministerio de Ciencia, Innovacion y Universidades of Spain RD16/0011/0021 (Red de Terapia Celular, TERCEL) Donal MacGrogan Alejandro Salguero-Jimenez Jose Luis de La Pompa; The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.S