Wrist worn raw-data accelerometers are used increasingly in large-scale population research. We examined whether sleep parameters can be estimated from these data in the absence of sleep diaries. Our ...heuristic algorithm uses the variance in estimated z-axis angle and makes basic assumptions about sleep interruptions. Detected sleep period time window (SPT-window) was compared against sleep diary in 3752 participants (range = 60-82 years) and polysomnography in sleep clinic patients (N = 28) and in healthy good sleepers (N = 22). The SPT-window derived from the algorithm was 10.9 and 2.9 minutes longer compared with sleep diary in men and women, respectively. Mean C-statistic to detect the SPT-window compared to polysomnography was 0.86 and 0.83 in clinic-based and healthy sleepers, respectively. We demonstrated the accuracy of our algorithm to detect the SPT-window. The value of this algorithm lies in studies such as UK Biobank where a sleep diary was not used.
It is now recognized that variations in the Δ17O of terrestrial materials resulting from purely mass dependent fractionations, though small, have geological significance. In this study, the δ18O and ...δ17O values of selected low temperature quartz and silica samples were measured in order to derive the quartz-water fractionation–temperature relationship for the three oxygen isotope system. A 18O/16O quartz-water fractionation equation valid for all temperatures was generated from published high temperature exchange experiments and low temperature empirical estimates and is given by 1000lnαqz-H2O18O/16O=4.20(0.11)×106T2-3.3(0.2)×1000T (T in Kelvins). The equilibrium δ17O–δ18O relationship is given by the equation lnα17O/16O=θlnα18O/16O. The variation of θ with temperature for the quartz-water system was determined empirically using low temperature marine diatoms, microcrystalline quartz and a modern sinter sample. A best fit to the data give the equation θSiO2–H2O=-(1.85±0.04)T+0.5305, indistinguishable from an earlier theoretical estimate.
Application of the quartz-water triple isotope system to low temperature samples provides constraints on both temperature and composition of the water with which the silica last equilibrated. Authigenic quartz crystallization temperatures cluster around 50°C, which are lower than many previous estimates. The combined δ18O and δ17O values of samples considered to be in equilibrium with ocean or meteoric waters can be used to estimate both formation temperatures and the δ18O value of the meteoric water. Unlike other multiple isotopes systems, such as combined H and O isotopes in cherts, the oxygen source and diagenetic potential for both 17O/16O and 18O/16O ratios are identical, simplifying interpretations from ancient samples.
Microbes are now well regarded for their important role in mammalian health. The microbiology of skin--a unique interface between the host and environment--is a major research focus in human health ...and skin disorders, but is less explored in other mammals. Here, we report on a cross-population study of the skin-associated bacterial community of humpback whales (Megaptera novaeangliae), and examine the potential for a core bacterial community and its variability with host (endogenous) or geographic/environmental (exogenous) specific factors. Skin biopsies or freshly sloughed skin from 56 individuals were sampled from populations in the North Atlantic, North Pacific and South Pacific oceans and bacteria were characterized using 454 pyrosequencing of SSU rRNA genes. Phylogenetic and statistical analyses revealed the ubiquity and abundance of bacteria belonging to the Flavobacteria genus Tenacibaculum and the Gammaproteobacteria genus Psychrobacter across the whale populations. Scanning electron microscopy of skin indicated that microbial cells colonize the skin surface. Despite the ubiquity of Tenacibaculum and Psychrobater spp., the relative composition of the skin-bacterial community differed significantly by geographic area as well as metabolic state of the animals (feeding versus starving during migration and breeding), suggesting that both exogenous and endogenous factors may play a role in influencing the skin-bacteria. Further, characteristics of the skin bacterial community from these free-swimming individuals were assembled and compared to two entangled and three dead individuals, revealing a decrease in the central or core bacterial community members (Tenacibaculum and Psychrobater spp.), as well as the emergence of potential pathogens in the latter cases. This is the first discovery of a cross-population, shared skin bacterial community. This research suggests that the skin bacteria may be connected to humpback health and immunity and could possibly serve as a useful index for health and skin disorder monitoring of threatened and endangered marine mammals.
The alteration of craniofacial structures has been associated with obstructive sleep apnoea (OSA). We hypothesised that: 1) a smaller mandible is a risk factor for OSA; and 2) the previously observed ...inferiorly positioned hyoid bone in apnoeics is associated with enlarged tongue volume. This is a case-control study using three-dimensional magnetic resonance imaging cephalometry. 55 apneics and 55 controls were matched for age, sex and race. The analysis was stratified by sex and controlled for age, race, height, neck visceral fat, skeletal type and tongue volume. We found that a 1-sd increase in mandibular length and depth were associated with decreased risk of sleep apnoea (OR 0.52, 95% CI 0.28-0.99 and OR 0.46, 95% CI 0.23-0.91, respectively) in males but not in females. Greater hyoid-to-nasion (OR 2.64, 95% CI 1.19-5.89 in males and OR 5.01, 95% CI 2.00-12.52 in females) and supramentale-to-hyoid (OR 2.39, 95% CI 1.12-5.14) in males and OR 3.38, 95% CI 1.49-7.68 in females) distances were associated with increased risk of OSA. The difference for hyoid position between apnoeics and controls was lost after controlling for tongue volume. Enlargement of tongue is likely to be the pathogenic factor for inferior-posterior positioning of hyoid. A small and shallow mandible is an independent risk factor for OSA in males but not in females.
Antiepileptic drugs (AEDs) may have adverse effects on bone mineral density (BMD) and metabolism. We previously reported biochemical evidence of increased bone turnover in premenopausal women with ...epilepsy on phenytoin monotherapy compared with those on carbamazepine, lamotrigine, and valproate. We therefore hypothesized that rates of bone loss would be higher in young women treated with phenytoin.
Ninety-three premenopausal women with epilepsy receiving a single AED (carbamazepine, lamotrigine, phenytoin, or valproate) participated. Subjects completed nutritional and physical activity questionnaires. Biochemical indices of bone and mineral metabolism and BMD of the proximal femur and lumbar spine were measured at baseline and 1 year.
Participants reported high calcium intake (>1,000 mg/day) and were physically active. Significant loss (2.6%) was seen at the femoral neck in the phenytoin group. BMD remained stable in the other AED groups. Bone turnover markers and calciotropic hormones were unchanged after 1 year in all groups except for a significant decline in urine N-telopeptide in the phenytoin group. In women receiving phenytoin, lower serum 25-hydroxyvitamin D concentrations were associated with higher parathyroid hormone, bone alkaline phosphatase, and urine N-telopeptide levels, a biochemical pattern consistent with secondary hyperparathyroidism and increased remodeling.
In this study, young women treated with phenytoin had significant femoral neck bone loss over 1 year. In contrast, those treated with carbamazepine, lamotrigine, and valproate did not have detectable adverse effects on bone turnover or bone mineral density. These results raise concerns about the long-term effects of phenytoin monotherapy on bone in young women with epilepsy.
Predictive habitat models can provide critical information that is necessary in many conservation applications. Using Maximum Entropy modeling, we characterized habitat relationships and generated ...spatial predictions of spinner dolphin (Stenella longirostris) resting habitat in the main Hawaiian Islands. Spinner dolphins in Hawai'i exhibit predictable daily movements, using inshore bays as resting habitat during daylight hours and foraging in offshore waters at night. There are growing concerns regarding the effects of human activities on spinner dolphins resting in coastal areas. However, the environmental factors that define suitable resting habitat remain unclear and must be assessed and quantified in order to properly address interactions between humans and spinner dolphins. We used a series of dolphin sightings from recent surveys in the main Hawaiian Islands and a suite of environmental variables hypothesized as being important to resting habitat to model spinner dolphin resting habitat. The model performed well in predicting resting habitat and indicated that proximity to deep water foraging areas, depth, the proportion of bays with shallow depths, and rugosity were important predictors of spinner dolphin habitat. Predicted locations of suitable spinner dolphin resting habitat provided in this study indicate areas where future survey efforts should be focused and highlight potential areas of conflict with human activities. This study provides an example of a presence-only habitat model used to inform the management of a species for which patterns of habitat availability are poorly understood.
Geochemical and isotopic data are presented for ~ 32 Ma-old high-K andesites and dacites from the Alpine Chain. The samples consist of plagioclase, amphibole, titanomagnetite and rare biotite and ...quartz. Geochemical and isotope data indicate that slab-derived fluids, sediment melts and presumably AFC processes involving continental crust played a key role in the petrogenesis of the high-K rocks. A contribution of fluids is suggested based on the overall enrichment of large-ion lithophile elements and related high Ba/La, Ba/Zr, Ba/Th, Ba/Nb and Pb/Nd, sometimes distinctively higher than average continental crust. Positively correlated Ba/Nb–Th/Nb relationships, low Ce/Pb, low Nb/U and a negative correlation of Pb isotopes with Ce/Pb and Nb/U and positive ∆ 7/4 and ∆ 8/4 values similar to GLOSS imply the additional involvement of a sediment-derived melt. Negatively correlated Nb/Ta–Zr/Hf ratios at overall low Nb/Ta (13–7.5) are best explained by parental magma differentiation involving amphibole and biotite in a continental arc system. The samples have moderately unradiogenic Nd (εNd: – 2.0 to – 6.7) and radiogenic
87
Sr/
86
Sr isotope compositions (0.7085–0.7113), moderately radiogenic Pb isotope compositions (
206
Pb/
204
Pb: 18.50–18.72;
207
Pb/
204
Pb: 15.59–15.65;
208
Pb/
204
Pb: 38.30–38.67), and elevated δ
18
O values (+ 6.5 to + 9.1 ‰). Epsilon Hf isotope values range from + 2.5 to – 4.0. Negative εHf(
t
) and εNd(
t
) values and
206
Pb/
204
Pb ratios are correlated with elevated K
2
O abundances that indicate enrichment in K
2
O is related to AFC processes. The offset of εHf at a given εNd points to involvement of aged garnet-bearing crustal lithologies. The latter feature is qualitatively consistent with modification of unexposed primary basaltic andesites by AFC processes involving deep crustal material. In conclusion, in an Alpine context, inferred unexposed primitive high-K basaltic to andesitic melts are generated in the mantle wedge through fluid infiltration from the descending slab where fluids may have caused also partial melting of sedimentary rocks that mixed with evolving andesite–dacite compositions towards shallow-level intrusive and extrusive rocks. High-K and related trace element and isotope features thus result from a combination of already elevated values with participation of fluids and melts and probably AFC processes.
Cerebral cavernous malformation is a common human vascular disease that arises due to loss-of-function mutations in genes encoding three intracellular adaptor proteins, cerebral cavernous ...malformations 1 protein (CCM1), CCM2, and CCM3. CCM1, CCM2, and CCM3 interact biochemically in a pathway required in endothelial cells during cardiovascular development in mice and zebrafish. The downstream effectors by which this signaling pathway regulates endothelial function have not yet been identified. Here we have shown in zebrafish that expression of mutant ccm3 proteins (ccm3Delta) known to cause cerebral cavernous malformation in humans confers cardiovascular phenotypes identical to those associated with loss of ccm1 and ccm2. CCM3Delta proteins interacted with CCM1 and CCM2, but not with other proteins known to bind wild-type CCM3, serine/threonine protein kinase MST4 (MST4), sterile 20-like serine/threonine kinase 24 (STK24), and STK25, all of which have poorly defined biological functions. Cardiovascular phenotypes characteristic of CCM deficiency arose due to stk deficiency and combined low-level deficiency of stks and ccm3 in zebrafish embryos. In cultured human endothelial cells, CCM3 and STK25 regulated barrier function in a manner similar to CCM2, and STKs negatively regulated Rho by directly activating moesin. These studies identify STKs as essential downstream effectors of CCM signaling in development and disease that may regulate both endothelial and epithelial cell junctions.
•Forms of progesterone differ between pregnant and non-pregnant humpback whales.•Progesterone was highest in the outer layer of blubber from female humpback whales.•Progesterone in males, lactating, ...and juvenile females was lower than pregnant humpbacks.•Pregnancy rates for both summer season and lactating whales were high in 2004–2006.•Resighting histories and physiology give synergistic insights to whale reproduction.
To better understand reproductive physiology of humpback whales Megaptera novaeangliae that reside in Hawai’i and Alaska, enzyme immunoassays were validated for both progesterone and testosterone in free-ranging and stranded animals (n = 185 biopsies). Concentrations were analyzed between different depths of large segments of blubber taken from skin to muscle layers of stranded female (n = 2, 1 pregnant, 1 non-pregnant) and male (n = 1) whales. Additionally, progesterone metabolites were identified between pregnant (n = 1) and non-pregnant (n = 3) females using high pressure liquid chromatography (HPLC). Progesterone concentrations were compared between juvenile (i.e., sexually immature), lactating, and pregnant females, and male whales, and pregnancy rates of sexually mature females were calculated. Based on replicate samples from ship struck animals collected at 7 depth locations, blubber containing the highest concentration of progesterone was located 1 cm below the skin for females, and the highest concentration of testosterone was in the skin layer of one male whale. HPLC of blubber samples of pregnant and non-pregnant females contain different immunoreactive progesterone metabolites, with the non-pregnant female eluate comprised of a more polar, and possibly conjugated, form of progesterone than the pregnant female. In females, concentrations of progesterone were highest in the blubber of pregnant (n = 28, 28.6 ± 6.9 ng/g), followed by lactating (n = 16, 0.9 ± 0.1 ng/g), and female juvenile (n = 5, 1.0 ± 0.2 ng/g) whales. Progesterone concentrations in male (n = 24, 0.6 ng/g ± 0.1 ng/g) tissues were the lowest all groups, and not different from lactating or juvenile females. Estimated summer season pregnancy rate among sexually mature females from the Hawai’i stock of humpback whales was 0.562 (95 % confidence interval 0.528–0.605). For lactating females, the year-round pregnancy rate was 0.243 (0.09–0.59), and varies depending on the threshold of progesterone assumed for pregnancy in the range between 3.1 and 28.5 ng/g. Our results demonstrate the synergistic value added when combining immunoreactive assays, HPLC, and long-term sighting histories to further knowledge of humpback whale reproductive physiology.
Abstract
Introduction:
Habitual short sleep duration is associated with adverse metabolic, cardiovascular, and inflammatory effects. Co-twin study methodologies account for familial (eg, genetics and ...shared environmental) confounding, allowing assessment of subtle environmental effects, such as the effect of habitual short sleep duration on gene expression. Therefore, we investigated gene expression in monozygotic twins discordant for actigraphically phenotyped habitual sleep duration.
Methods:
Eleven healthy monozygotic twin pairs (82% female; mean age 42.7 years; SD = 18.1), selected based on subjective sleep duration discordance, were objectively phenotyped for habitual sleep duration with 2 weeks of wrist actigraphy. Peripheral blood leukocyte (PBL) RNA from fasting blood samples was obtained on the final day of actigraphic measurement and hybridized to Illumina humanHT-12 microarrays. Differential gene expression was determined between paired samples and mapped to functional categories using Gene Ontology. Finally, a more comprehensive gene set enrichment analysis was performed based on the entire PBL transcriptome.
Results:
The mean 24-hour sleep duration of the total sample was 439.2 minutes (SD = 46.8 minutes; range 325.4–521.6 minutes). Mean within-pair sleep duration difference per 24 hours was 64.4 minutes (SD = 21.2; range 45.9–114.6 minutes). The twin cohort displayed distinctive pathway enrichment based on sleep duration differences. Habitual short sleep was associated with up-regulation of genes involved in transcription, ribosome, translation, and oxidative phosphorylation. Unexpectedly, genes down-regulated in short sleep twins were highly enriched in immuno-inflammatory pathways such as interleukin signaling and leukocyte activation, as well as developmental programs, coagulation cascade, and cell adhesion.
Conclusions:
Objectively assessed habitual sleep duration in monozygotic twin pairs appears to be associated with distinct patterns of differential gene expression and pathway enrichment. By accounting for familial confounding and measuring real life sleep duration, our study shows the transcriptomic effects of habitual short sleep on dysregulated immune response and provides a potential link between sleep deprivation and adverse metabolic, cardiovascular, and inflammatory outcomes.
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