Near-infrared spectroscopy as a tool for marine mammal research and care

This project was partially funded by the Department for Business, Energy and Industrial Strategy Offshore Energy Strategic Environmental Assessment Programme. Supplementary funding supporting JM was provided by the US Office of Naval Research (ONR) grant nos. N00014-18-1-2062 and N00014-20-1-2709. Supplementary funding supporting AF and JM was provided by the US Office of Naval Research (ONR) grant no. N00014-19-1-2560. Supplementary funding supporting BS-C, JK, and AR was provided by the US Office of Naval Research (ONR) grant no. N00014-19-1-1223.Developments in wearable human medical and sports health trackers has offered new solutions to challenges encountered by eco-physiologists attempting to measure physiological attributes in freely moving animals. Near-infrared spectroscopy (NIRS) is one such solution that has potential as a powerful physio-logging tool to assess physiology in freely moving animals. NIRS is a non-invasive optics-based technology, that uses non-ionizing radiation to illuminate biological tissue and measures changes in oxygenated and deoxygenated hemoglobin concentrations inside tissues such as skin, muscle, and the brain. The overall footprint of the device is small enough to be deployed in wearable physio-logging devices. We show that changes in hemoglobin concentration can be recorded from bottlenose dolphins and gray seals with signal quality comparable to that achieved in human recordings. We further discuss functionality, benefits, and limitations of NIRS as a standard tool for animal care and wildlife tracking for the marine mammal research community.Publisher PDFPeer reviewe

Quinolone signaling in the cell-to-cell communication system of Pseudomonas aeruginosa

Numerous species of bacteria use an elegant regulatory mechanism known as quorum sensing to control the expression of specific genes in a cell-density dependent manner. In Gram-negative bacteria, quorum sensing systems function through a cell-to-cell signal molecule (autoinducer) that consists of a homoserine lactone with a fatty acid side chain. Such is the case in the opportunistic human pathogen Pseudomonas aeruginosa, which contains two quorum sensing systems (las and rhl) that operate via the autoinducers, N-(3-oxododecanoyl)-L-homoserine lactone and N-butyryl-Lhomoserine lactone. The study of these signal molecules has shown that they bind to and activate transcriptional activator proteins that specifically induce numerous P. aeruginosa virulence genes. We report here that P. aeruginosa produces another signal molecule, 2-heptyl-3-hydroxy-4-quinolone, which has been designated as the Pseudomonas quinolone signal. It was found that this unique cell-to-cell signal controlled the expression of lasB, which encodes for the major virulence factor, LasB elastase. We also show that the synthesis and bioactivity of Pseudomonas quinolone signal were mediated by the P. aeruginosa las and rhl quorum sensing systems, respectively. The demonstration that 2-heptyl-3- hydroxy-4-quinolone can function as an intercellular signal sheds light on the role of secondary metabolites and shows that P. aeruginosa cell-to-cell signaling is not restricted to acyl-homoserine lactones. Originally published Proc. Natl. Acad. Sci, Vol. 96, No. 20, Sep. 199

Evaluating feasibility of functional near-infrared spectroscopy in dolphins

SIGNIFICANCE: Using functional near-infrared spectroscopy (fNIRS) in bottlenose dolphins (Tursiops truncatus) could help to understand how echolocating animals perceive their environment and how they focus on specific auditory objects, such as fish, in noisy marine settings. AIM: To test the feasibility of near-infrared spectroscopy (NIRS) in medium-sized marine mammals, such as dolphins, we modeled the light propagation with computational tools to determine the wavelengths, optode locations, and separation distances that maximize sensitivity to brain tissue. APPROACH: Using frequency-domain NIRS, we measured the absorption and reduced scattering coefficient of dolphin sculp. We assigned muscle, bone, and brain optical properties from the literature and modeled light propagation in a spatially accurate and biologically relevant model of a dolphin head, using finite-element modeling. We assessed tissue sensitivities for a range of wavelengths (600 to 1700 nm), source-detector distances (50 to 120 mm), and animal sizes (juvenile model 25% smaller than adult). RESULTS: We found that the wavelengths most suitable for imaging the brain fell into two ranges: 700 to 900 nm and 1100 to 1150 nm. The optimal location for brain sensing positioned the center point between source and detector 30 to 50 mm caudal of the blowhole and at an angle 45 deg to 90 deg lateral off the midsagittal plane. Brain tissue sensitivity comparable to human measurements appears achievable only for smaller animals, such as juvenile bottlenose dolphins or smaller species of cetaceans, such as porpoises, or with source-detector separations ≫100  mm in adult dolphins. CONCLUSIONS: Brain measurements in juvenile or subadult dolphins, or smaller dolphin species, may be possible using specialized fNIRS devices that support optode separations of >100  mm. We speculate that many measurement repetitions will be required to overcome hemodynamic signals originating predominantly from the muscle layer above the skull. NIRS measurements of muscle tissue are feasible today with source-detector separations of 50 mm, or even less.Publisher PDFPeer reviewe

Associations of Plasma Phospholipid and Dietary Alpha Linolenic Acid With Incident Atrial Fibrillation in Older Adults: The Cardiovascular Health Study

Background: Few studies have examined the relationship of α‐linolenic acid (ALA 18:3n‐3), an intermediate‐chain essential n‐3 polyunsaturated fatty acid derived from plants and vegetable oils, with incident atrial fibrillation (AF). Methods and Results: The study population included participants from the Cardiovascular Health Study, a community‐based longitudinal cohort of adults aged 65 or older, free of prevalent coronary heart disease and atrial fibrillation. We assessed the associations of plasma phospholipid and dietary ALA with incident AF using Cox regression. The biomarker analysis comprised a total of 2899 participants, and the dietary analysis comprised 4337 participants. We found no association of plasma phospholipid ALA and incident AF. Comparing each of the second, third, and fourth quartiles to the lowest quartile, the hazard ratios for AF were 1.11 (95% CI, 0.90 to 1.37), 1.09 (95% CI, 0.88 to 1.35), and 0.92 (95% CI, 0.74 to 1.15), after adjustment for age, sex, race, clinic, education, smoking, alcohol, body mass index, waist circumference, diabetes, heart failure, stroke, treated hypertension, and physical activity (P trend=0.48). When dietary ALA was considered the exposure of interest, results were similar. Conclusions: Results from this prospective cohort study of older adults indicate no association of plasma phospholipid or dietary ALA and incident AF

Plasma Phospholipid Saturated Fatty Acids and Incident Atrial Fibrillation: The Cardiovascular Health Study

Background: Prior studies suggest that circulating fatty acids may influence the risk of atrial fibrillation (AF), but little is known about the associations of circulating saturated fatty acids with risk of AF. Methods and Results: The study population included 2899 participants from the Cardiovascular Health Study, a community‐based longitudinal cohort of adults aged 65 years or older in the United States who were free of prevalent coronary heart disease and AF in 1992. Cox regression was used to assess the association of all the long‐chain saturated fatty acids—palmitic acid (16:0), stearic acid (18:0), arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0)—with incident AF. During a median of 11.2 years of follow‐up, 707 cases of incident AF occurred. After adjustment for other AF risk factors, higher levels of circulating 16:0 were associated with a higher risk of AF (hazard ratio comparing highest and lowest quartiles: 1.48; 95% CI: 1.18, 1.86). In contrast, higher levels of circulating 18:0, 20:0, 22:0, and 24:0 were each associated with a lower risk of AF. The hazard ratios (95% CI) for AF in the top and bottom quartiles were 0.76 (95% CI: 0.61, 0.95) for 18:0; 0.78 (95% CI: 0.63, 0.97) for 20:0; 0.62 (95% CI: 0.50, 0.78) for 22:0; and 0.68 (95% CI: 0.55, 0.85) for 24:0. Conclusions: Results from this prospective cohort study of older adults demonstrate divergent associations of circulating 16:0 versus longer‐chain saturated fatty acids with incident AF, highlighting the need to investigate both determinants of these levels and potential pathways of the observed differential risk

Behavior of QQ-Plots and Genomic Control in Studies of Gene-Environment Interaction

Genome-wide association studies of gene-environment interaction (GxE GWAS) are becoming popular. As with main effects GWAS, quantile-quantile plots (QQ-plots) and Genomic Control are being used to assess and correct for population substructure. However, in GE work these approaches can be seriously misleading, as we illustrate; QQ-plots may give strong indications of substructure when absolutely none is present. Using simulation and theory, we show how and why spurious QQ-plot inflation occurs in GE GWAS, and how this differs from main-effects analyses. We also explain how simple adjustments to standard regression-based methods used in GE GWAS can alleviate this problem

Myocardial infarction and stroke associated with diuretic based two drug antihypertensive regimens: population based case-control study

Objective To examine the association of myocardial infarction and stroke incidence with several commonly used two drug antihypertensive treatment regimens

Generalized estimating equations for genome-wide association studies using longitudinal phenotype data

Many longitudinal cohort studies have both genome-wide measures of genetic variation and repeated measures of phenotypes and environmental exposures. Genome-wide association study analyses have typically used only cross-sectional data to evaluate quantitative phenotypes and binary traits. Incorporation of repeated measures may increase power to detect associations, but also requires specialized analysis methods. Here we discuss one such method – generalized estimating equations (GEE) – in the contexts of analysis of main effects of rare genetic variants and analysis of gene-environment interactions. We illustrate the potential for increased power using GEE analyses instead of cross-sectional analyses. We also address challenges that arise, such as the need for small-sample corrections when the minor allele frequency of a genetic variant and/or the prevalence of an environmental exposure is low. To illustrate methods for detection of gene-drug interactions on a genome-wide scale, using repeated measures data, we conduct single-study analyses and meta-analyses across studies in three large cohort studies participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium – the Atherosclerosis Risk in Communities (ARIC) study, the Cardiovascular Health Study (CHS), and the Rotterdam Study (RS)