Maternal dietary levels of one-carbon (1C) metabolites (folic acid and choline) during pregnancy play a vital role in neurodevelopment. However, the impact of maternal dietary deficiencies on ...offspring stroke outcomes later in life remains undefined. The aim of this study was to investigate the role of maternal dietary deficiencies in folic acid and choline on ischemic stroke outcomes in middle-aged offspring. Female mice were maintained on either a control or deficient diet prior to and during pregnancy and lactation. At 10 months of age ischemic stroke was induced in male and female offspring. Stroke outcome was assessed by measuring motor function and brain tissue. There was no difference in offspring motor function; however, sex differences were present. In brain tissue, maternal dietary deficiency increased ischemic damage volume and offspring from deficient mothers had reduced neurodegeneration and neuroinflammation within the ischemic region. Furthermore, there were changes in plasma 1C metabolites as a result of maternal diet and sex. Our data indicate that maternal dietary deficiencies do not impact offspring behavior after ischemic stroke but do play a role in brain histology and one-carbon metabolite levels in plasma. Additionally, this study demonstrates that the sex of mice plays an important role in stroke outcomes.
The purpose of this study was to evaluate the effect of outside-field-of-view (FOV) lead shielding on the entrance surface dose (ESD) of the breast on an anthropomorphic X-ray phantom for a variety ...of axial skeleton X-ray examinations.
Using an anthropomorphic phantom and radiation dosimeter, the ESD of the breast was measured with and without outside-FOV shielding in anterior-posterior (AP) abdomen, AP cervical spine, occipitomental 30° (OM30) facial bones, AP lumbar spine, and lateral lumbar spine radiography. The effect of several exposure parameters, including a low milliampere-seconds technique, grid use, automatic exposure control use, wraparound lead (WAL) use, trolley use, and X-ray table use, on the ESD of the breast with and without outside-FOV shielding was investigated. The mean ESD (μSv) and standard deviation for each radiographic protocol were calculated. A one-tailed Student's t-test was carried out to evaluate whether ESD to the breast was reduced with the use of outside-FOV shielding.
A total of 920 breast ESD measurements were recorded across the different protocol parameters. The largest decrease in mean ESD of the breast with outside-FOV shielding was 0.002 μSv (
= 0.084), recorded in the AP abdomen on the table with a grid, OM30 on the table with a grid, OM30 standard protocol on the trolley, and OM30 on the trolley with WAL protocols. This decrease was found to be statistically non-significant.
This study found no significant decrease in the ESD of the breast with the use of outside-FOV shielding for the AP abdomen, AP cervical spine, OM30 facial bones, AP lumbar spine, or lateral lumbar spine radiography across a range of protocols.
Maternal one-carbon metabolism plays an important role in early life programming. There is a well-established connection between the fetal environment and the health status of the offspring. However, ...there is a knowledge gap on how maternal nutrition impacts stroke outcomes in offspring. The aim of our study was to investigate the role of maternal dietary deficiencies in folic acid or choline on stroke outcomes in 3-month-old offspring. Adult female mice were fed a folic acid-deficient diet, choline-deficient diet, or control diet 4 weeks before pregnancy. They were continued on diets during pregnancy and lactation. Male and female offspring were weaned onto a control diet and at 2 months of age were subjected to ischemic stroke within the sensorimotor cortex via photothrombotic damage. Mothers maintained on either a folic acid-deficient diet or choline-deficient diet had reduced levels of S-adenosylmethionine in the liver and S-adenosylhomocysteine in the plasma. After ischemic stroke, motor function was impaired in 3-month-old offspring from mothers receiving either a folic acid-deficient diet or choline-deficient diet compared to the animals receiving a control diet. In brain tissue, there was no difference in ischemic damage volume. When protein levels were assessed in ischemic brain tissue, there were lower levels of active caspase-3 and hypoxia-inducible factor 1α in males compared to females and betaine levels were reduced in offspring from the mothers receiving a choline-deficient diet. Our results demonstrate that a deficient maternal diet at critical time points in neurodevelopment results in worse stroke outcomes. This study emphasizes the importance of maternal diet and the impact it can have on offspring health.
Abstract only Maternal one-carbon metabolism, including dietary levels of folic acid and choline, play an important role in early life programming. There is a well-established connection between the ...fetal environment and the health status of offspring. However, there is a gap in knowledge on how maternal nutrition will affect the health status of the offspring after a cardiovascular event like ischemic stroke. The aim of our study was to investigate the role of maternal dietary deficiencies in folic acid or choline on stroke outcome in 3- and 10-month-old male and female offspring. Adult female mice were fed a folic acid deficient diet (FADD), a choline deficient diet (ChDD), or a control diet (CD) four weeks prior to pregnancy to deplete stores, they were continued on diets during pregnancy and lactation. Male and female offspring were weaned onto a control diet and at 2 or 10 months of age were subject to ischemic stroke within the sensorimotor cortex via the photothrombosis ischemic damage model. At 3 or 11 months of age, motor function was measured in offspring and tissue was collected for analysis. Mothers maintained on either a FADD or ChDD had reduced levels of S -adenosylmethionine in liver tissue compared to controls. In offspring after ischemic stroke, motor function was impaired in 3-month-old male and female offspring from deficient mothers compared to control diet offspring. In 11-month-old mice there was no impact of maternal diet on motor function, but we observed sex differences. Male middle-aged adult mice had worse motor function compared to female offspring. In brain tissue, there was no impact of maternal diet on ischemic damage volume in 3-month-old animals. Interestingly, maternal diet impacted ischemic damage in 10-month-old male and female offspring. Neurodegeneration and choline metabolism in ischemic brain tissue was also impacted in 3 and 11-month-old offspring. The findings of our study suggest that a maternal diet deficient in either choline or folic acid impacts stroke outcome in young animals compared to middle-aged animals. These results points to the important role of the maternal diet in early life programming, while emphasizing its effects on both fetal development and long-term cerebrovascular health.
The physical properties of
in vitro
iron-reconstituted and genetically engineered human heteropolymer ferritins were investigated. High-angle annular dark-field scanning transmission electron ...microscopy (HAADF-STEM), electron energy-loss spectroscopy (EELS), and
57
Fe Mössbauer spectroscopy were employed to ascertain (1) the microstructural, electronic, and micromagnetic properties of the nanosized iron cores, and (2) the effect of the H and L ferritin subunit ratios on these properties. Mössbauer spectroscopic signatures indicate that all iron within the core is in the high spin ferric state. Variable temperature Mössbauer spectroscopy for H-rich (H
21
/L
3
) and L-rich (H
2
/L
22
) ferritins reconstituted at 1000
57
Fe/protein indicates superparamagnetic behavior with blocking temperatures of 19 K and 28 K, while HAADF-STEM measurements give average core diameters of (3.7 ± 0.6) nm and (5.9 ± 1.0) nm, respectively. Most significantly, H-rich proteins reveal elongated, dumbbell, and crescent-shaped cores, while L-rich proteins present spherical cores, pointing to a correlation between core shape and protein shell composition. Assuming an attempt time for spin reversal of
τ
0
= 10
−11
s, the Néel-Brown formula for spin-relaxation time predicts effective magnetic anisotropy energy densities of 6.83 × 10
4
J m
−3
and 2.75 × 10
4
J m
−3
for H-rich and L-rich proteins, respectively, due to differences in surface and shape contributions to magnetic anisotropy in the two heteropolymers. The observed differences in shape, size, and effective magnetic anisotropies of the derived biomineral cores are discussed in terms of the iron nucleation sites within the interior surface of the heteropolymer shells for H-rich and L-rich proteins. Overall, our results imply that site-directed nucleation and core growth within the protein cavity play a determinant role in the resulting core morphology. Our findings have relevance to iron biomineralization processes in nature and the growth of designer's magnetic nanoparticles within recombinant apoferritin nano-templates for nanotechnology.
The physical properties of
in vitro
iron-reconstituted and genetically engineered human heteropolymer ferritins were investigated.
Reservoir computing is a machine learning framework where the readouts from a nonlinear system (the reservoir) are trained so that the output from the reservoir, when forced with an input signal, ...reproduces a desired output signal. A common implementation of reservoir computers is to use a recurrent neural network as the reservoir. The design of this network can have significant effects on the performance of the reservoir computer. In this paper we study the effect of the node activation function on the ability of reservoir computers to learn and predict chaotic time series. We find that the Forecast Horizon (FH), the time during which the reservoir's predictions remain accurate, can vary by an order of magnitude across a set of 16 activation functions used in machine learning. By using different functions from this set, and by modifying their parameters, we explore whether the entropy of node activation levels or the curvature of the activation functions determine the predictive ability of the reservoirs. We find that the FH is low when the activation function is used in a region where it has low curvature, and a positive correlation between curvature and FH. For the activation functions studied we find that the largest FH generally occurs at intermediate levels of the entropy of node activation levels. Our results show that the performance of reservoir computers is very sensitive to the activation function shape. Therefore, modifying this shape in hyperparameter optimization algorithms can lead to improvements in reservoir computer performance.
Although endothelial cells and keratinocytes appear to be the primary cellular targets of sulfur mustard (SM), the role of the nuclear enzyme poly (ADP-ribose) polymerase (PARP) in SM-induced ...vesication has not been clearly defined. PARP is thought to play a crucial role in DNA repair mechanisms following exposure to alkylating agents like SM. Using a combination of fluorescence microscopy and biochemical assays, we tested the hypothesis that SM causes activation of PARP in endothelial cells and keratinocytes with subsequent loss of nicotinamide adenine dinucleotide (NAD) and depletion of adenosine triphosphate (ATP) levels. To determine if PARP activation accounts for SM-induced vesication, keratinocyte adherence and permeability of endothelial monolayers were measured as in vitro correlates of vesication. As early as 2 to 3 h after exposure to SM concentrations as low as 250 microM, dramatic changes were induced in keratinocyte morphology and microfilament architecture. Exposure to 500 microM SM induced a fourfold increase in PARP activity in endothelial cells, and a two- to threefold increase in keratinocytes. SM induced a dose-related loss of NAD+ in both endothelial cells and keratinocytes. ATP levels fell to approximately 50% of control levels in response to SM concentrations >/=500 microM. SM concentrations >/=250 microM significantly reduced keratinocyte adherence as early as 3 h after exposure. Endothelial monolayer permeability increased substantially with concentrations of SM >250 microM. These observations support the hypothesis that the pathogenic events necessary for SM-induced vesication (i.e., capillary leak and loss of keratinocyte adherence) at higher vesicating doses of SM (>/=500 microM) may depend on NAD loss with PARP activation and subsequent ATP-dependent effects on microfilament architecture. Vesication developing as a result of exposure to lower concentrations of SM presumably occurs by mechanisms that do not depend on loss of cellular ATP (e.g., apoptosis and direct SM-mediated damage to integrins and the basement membrane).
