Perennial water storage in firn aquifers has been observed within the lower percolation zone of the southeast Greenland ice sheet. Spatially distributed seismic and radar observations, made ~50 km ...upstream of the Helheim Glacier terminus, reveal spatial variations of seismic velocity within a firn aquifer. From 1.65 to 1.8 km elevation, shear‐wave velocity (Vs) is 1,290 ± 180 m/s in the unsaturated firn, decreasing below the water table (~15 m depth) to 1,130 ± 250 m/s. Below 1.65 km elevation, Vs in the saturated firn is 1,270 ± 220 m/s. The compressional‐to‐shear velocity ratio decreases in the downstream saturated zone, from 2.30 ± 0.54 to 2.01 ± 0.46, closer to its value for pure ice (2.00). Consistent with colocated firn cores, these results imply an increasing concentration of ice in the downstream sites, reducing the porosity and storage potential of the firn likely caused by episodic melt and freeze during the evolution of the aquifer.
Plain Language Summary
An integrated geophysical analysis of seismic, radar, and borehole measurements has been completed over a firn aquifer in southeast Greenland. We show the stiffness of the aquifer increases at lower elevations, closer to sea level, which leads to a decrease in pore space for the meltwater to be stored. This corresponds to an increase in ice content within the firn at lower elevations, as observed in borehole measurements, and likely caused by the meltwater refreezing within and below the aquifer.
Key Points
Characterizing the storage potential of firn aquifers is important for predicting water budgets in a warming world
Multiple geophysical methods are combined to evaluate the elastic properties and porosity of the firn aquifer
Seismic velocities detect an increase in ice content in the aquifer downslope, reducing the porosity and storage potential of the firn
Background: Vitamin K mediates the gamma-carboxylation of glutamyl residues on several bone proteins, notably osteocalcin. High serum concentrations of undercarboxylated osteocalcin and low serum ...concentrations of vitamin K are associated with lower bone mineral density and increased risk of hip fracture. However, data are limited on the effects of dietary vitamin K. Objective: We investigated the hypothesis that high intakes of vitamin K are associated with a lower risk of hip fracture in women. Design: We conducted a prospective analysis within the Nurses' Health Study cohort. Diet was assessed in 72327 women aged 38-63 y with a food-frequency questionnaire in 1984 (baseline). During the subsequent 10 y of follow-up, 270 hip fractures resulting from low or moderate trauma were reported. Results: Women in quintiles 2-5 of vitamin K intake had a significantly lower age-adjusted relative risk (RR: 0.70; 95% CI: 0.53, 0.93) of hip fracture than women in the lowest quintile (< 109 microgram/d). Risk did not decrease between quintiles 2 and 5 and risk estimates were not altered when other risk factors for osteoporosis, including calcium and vitamin D intakes, were added to the models. Risk of hip fracture was also inversely associated with lettuce consumption (RR: 0.55; 95% CI: 0.40, 0.78) for one or more servings per day compared with one or fewer servings per week), the food that contributed the most to dietary vitamin K intakes. Conclusions: Low intakes of vitamin K may increase the risk of hip fracture in women. The data support the suggestion for a reassessment of the vitamin K requirements that are based on bone health and blood coagulation.
Low dietary vitamin K intake has been associated with an increased risk of hip fracture in men and women. Few data exist on the association between dietary vitamin K intake and bone mineral density ...(BMD).
We studied cross-sectional associations between self-reported dietary vitamin K intake and BMD of the hip and spine in men and women aged 29-86 y.
BMD was measured at the hip and spine in 1112 men and 1479 women (macro x +/- SD age: 59 +/- 9 y) who participated in the Framingham Heart Study (1996-2000). Dietary and supplemental intakes of vitamin K were assessed with the use of a food-frequency questionnaire. Additional covariates included age, body mass index, smoking status, alcohol use, physical activity score, and menopause status and current estrogen use among the women.
Women in the lowest quartile of vitamin K intake (macro x: 70.2 microg/d) had significantly (P < or = 0.005) lower mean (+/- SEM) BMD at the femoral neck (0.854 +/- 0.006 g/cm(2)) and spine (1.140 +/- 0.010 g/cm(2)) than did those in the highest quartile of vitamin K intake (macro x: 309 microg/d): 0.888 +/- 0.006 and 1.190 +/- 0.010 g/cm(2), respectively. These associations remained after potential confounders were controlled for and after stratification by age or supplement use. No significant association was found between dietary vitamin K intake and BMD in men.
Low dietary vitamin K intake was associated with low BMD in women, consistent with previous reports that low dietary vitamin K intake is associated with an increased risk of hip fracture. In contrast, there was no association between dietary vitamin K intake and BMD in men.
In 2018, it was estimated that fewer than 20 of Mexico’s endemic vaquita porpoise
Phocoena sinus
remained, and the species was declining by 47% yr
-1
. Entanglement in gillnets is the sole threat to ...the species, and since the last population size estimate, gillnetting has increased in the small area where most vaquitas remain—a 12 × 24 km area in the Gulf of California near San Felipe, Mexico. We conducted research efforts in 2019 and 2021 in that area to estimate the minimum numbers of adults and calves and look for any signs that vaquitas are unhealthy. Through expert elicitation, we estimated between 7 and 15 unique individuals were seen in 2019 and 5-13 were seen in 2021. Calves were seen in both years, and all vaquitas appeared healthy. Population projections from the last full survey indicated that more vaquitas have survived than expected. We suggest that these surviving adult vaquitas may have learned to avoid entanglement in gillnets. These vaquitas and their calves provide hope that the species can survive. However, given the high levels of illegal gillnetting and the theft of equipment which hindered our monitoring efforts, and with only around 10 individuals remaining, survival can only be assured if vaquita habitat is made gillnet-free.
BACKGROUND AND PURPOSE The P2X7 receptor is implicated in inflammation and pain and is therefore a potential target for therapeutic intervention. Here, the development of a native tissue radioligand ...binding, localization and ex vivo occupancy assay for centrally penetrant P2X7 receptor antagonists is described.
EXPERIMENTAL APPROACH Autoradiography studies using the P2X7 antagonist radioligand 3H‐A‐804598 were carried out in rat brain and spinal cord. Subsequent in vitro binding and ex vivo occupancy assays were performed using rat cortex homogenate.
KEY RESULTS P2X7 expression was shown to be widespread throughout the rat brain, and in the grey matter of the spinal cord. In binding assays in rat cortex homogenate, ∼60% specific binding was achieved at equilibrium. In kinetic binding assays, kon and koff values of 0.0021·min−1·nM−1 and 0.0070·min−1 were determined, and the Kd derived from kinetic measurements was consistent with that derived from saturation analysis. Novel P2X7 antagonists inhibited the binding of 3H‐A‐804598 to rat cortex P2X7 receptors with Ki values of <40 nM. In an ex vivo occupancy assay, a P2X7 antagonist dosed orally to rats caused a concentration‐dependent inhibition of the specific binding of 3H‐A‐804598 to rat cortex.
CONCLUSIONS AND IMPLICATIONS The present study describes the development of an assay that allows localization of P2X7 receptors, the measurement of the binding affinity of P2X7 receptor antagonists in native tissue, and provides a means of determining central P2X7 receptor occupancy. These assays could form an important part of a P2X7 drug discovery programme.
Summary
To determine the association of the Apolipoprotein E (APOE)
E4
gene polymorphism with bone mineral density (BMD) and fractures we conducted a meta-analysis of 17 reports. Despite lower ...trochanteric and lumbar BMD in
APOE4
carriers, there is insufficient evidence to support a consistent association of
APOE
with bone health.
Introduction
APOE has been studied for its potential role in osteoporosis risk. It is hypothesized that genetic variation at
APOE
locus, known as
E2
,
E3
, and
E4
, may modulate BMD through its effects on lipoproteins and vitamin K transport. The purpose of this study was to determine the association of the
APOE-E4
gene polymorphism with bone-related phenotypes.
Methods
We conducted a meta-analysis that combined newly analyzed individual data from two community-based cohorts, the Framingham Offspring Study (
N
= 1,495) and the vitamin K clinical trial (
N
= 377), with 15 other eligible published reports. Bone phenotypes included BMD measurements of the hip (total hip and trochanteric and femoral neck sites) and lumbar spine (from the L2 to L4 vertebrae) and prevalence or incidence of vertebral, hip, and other fractures.
Results
In sex-pooled analyses,
APOE4
carriers had a 0.018 g/cm
2
lower weighted mean trochanteric BMD than non carriers (
p
= 0.0002) with no evidence for between-study heterogeneity. A significant association was also detected with lumbar spine BMD (
p
= 0.006); however, inter-study heterogeneity was observed. Associations with lumbar spine and trochanteric BMD were observed predominantly in women and became less significant in meta-regression (
p
= 0.055 and 0.01, respectively). There were no consistent associations of
APOE4
genotype with BMD at other skeletal sites or with fracture risk.
Conclusions
Based on these findings, there is insufficient evidence to support a strong and consistent association of the
APOE
genotype with BMD and fracture incidence.
Objective: To investigate ecological correlates of the development of overweight in a multisite study sample of children followed from age 2 to 12. Design: Longitudinal examination of covariates of ...overweight status throughout childhood, with covariates drawn from three ecological levels: sociocultural or demographic, quality of the child's home environment, and proximal child experience that could directly affect the balance between energy intake and energy expenditure. Subjects: A total of 960 children participating in a long-term longitudinal study provided growth data at least once; 653 of the children had complete data on covariates. Measurements: Height and weight measured seven times between ages 2 and 12 were converted to a body mass index (BMI) and entered into a latent transition analysis to identify patterns of overweight across childhood. Ecological correlates measured longitudinally included demographic characteristics obtained by maternal report, home environment quality obtained by observation and maternal report, and proximal child experience factors obtained by observation, maternal report and child report. Results: Four patterns of overweight were found: never overweight, overweight beginning at preschool age, overweight beginning in elementary school, and return to normal weight after being overweight at preschool age. The weight status groups differed on home environment quality and proximal child experience factors but not on demographics. Children overweight at preschool had less sensitive mothers than never overweight children. Children overweight at school age had fewer opportunities for productive activity at home than did never overweight children. School-age overweight children also watched the most TV after school. Multivariate logistic regression analyses further indicated the significance to children's weight status of proximal child experience variables. Less physically active children and those who watched more television after school were more likely to become overweight. Results did not vary by child sex. Conclusion: The results support the idea that childhood overweight is multiply determined. The one potentially important and changeable factor identified as a target for intervention centers on how children spend their time, especially their after-school time. Children who are more physically active and spend less time watching TV after school are less likely to become overweight by age 12.
Oxidative stress is believed to be the cause of cell death in multiple disorders of the brain, including perinatal hypoxia/ischemia. Glutamate, cystine deprivation, homocysteic acid, and the ...glutathione synthesis inhibitor buthionine sulfoximine all cause oxidative injury to immature neurons and oligodendrocytes by depleting intracellular glutathione. Although vitamin K is not a classical antioxidant, we report here the novel finding that vitamin K1 and K2 (menaquinone-4) potently inhibit glutathione depletion-mediated oxidative cell death in primary cultures of oligodendrocyte precursors and immature fetal cortical neurons with EC50 values of 30 nm and 2 nm, respectively. The mechanism by which vitamin K blocks oxidative injury is independent of its only known biological function as a cofactor for gamma-glutamylcarboxylase, an enzyme responsible for posttranslational modification of specific proteins. Neither oligodendrocytes nor neurons possess significant vitamin K-dependent carboxylase or epoxidase activity. Furthermore, the vitamin K antagonists warfarin and dicoumarol and the direct carboxylase inhibitor 2-chloro-vitamin K1 have no effect on the protective function of vitamin K against oxidative injury. Vitamin K does not prevent the depletion of intracellular glutathione caused by cystine deprivation but completely blocks free radical accumulation and cell death. The protective and potent efficacy of this naturally occurring vitamin, with no established clinical side effects, suggests a potential therapeutic application in preventing oxidative damage to undifferentiated oligodendrocytes in perinatal hypoxic/ischemic brain injury.
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