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Early life adversity (ELA) has been associated with inflammation and immunosenescence, as well as hyporeactivity of the HPA axis. Because the immune system and the HPA axis are tightly intertwined around the glucocorticoid receptor (GR), we examined peripheral GR functionality in the EpiPath cohort among participants who either had been exposed to ELA (separation from parents and/or institutionalization followed by adoption; n = 40) or had been reared by their biological parents (n = 72).
Expression of the strict GR target genes FKBP5 and GILZ as well as total and 1F and 1H GR transcripts were similar between groups. Furthermore, there were no differences in GR sensitivity, examined by the effects of dexamethasone on IL6 production in LPS-stimulated whole blood. Although we did not find differences in methylation at the GR 1F exon or promoter region, we identified a region of the GR 1H promoter (CpG 1-9) that showed lower methylation levels in ELA.
Our results suggest that peripheral GR signaling was unperturbed in our cohort and the observed immune phenotype does not appear to be secondary to an altered GR response to the perturbed HPA axis and glucocorticoid (GC) profile, although we are limited in our measures of GR activity and time points.
In this study, we report the characterization of a 304L stainless steel cylindrical projectile produced by additive manufacturing. The projectile was compressively deformed using a Taylor Anvil Gas Gun, leading to a huge strain gradient along the axis of the deformed cylinder. Spatially resolved neutron diffraction measurements on the HIgh Pressure Preferred Orientation time-of-flight diffractometer (HIPPO) and Spectrometer for Materials Research at Temperature and Stress diffractometer (SMARTS) beamlines at the Los Alamos Neutron Science CEnter (LANSCE) with Rietveld and single-peak analysis were used to quantitatively evaluate the volume fractions of the α, γ, and ε phases as well as residual strain and texture. The texture of the γ phase is consistent with uniaxial compression, while the α texture can be explained by the Kurdjumov–Sachs relationship from the γ texture after deformation. This indicates that the material first deformed in the γ phase and subsequently transformed at larger strains. The ε phase was only found in volumes close to the undeformed material with a texture connected to the γ texture by the Shoji–Nishiyama orientation relationship. This allows us to conclude that the ε phase occurs as an intermediate phase at lower strain, and is superseded by the α phase when strain increases further. We found a proportionality between the root-mean-squared microstrain of the γ phase, dominated by the dislocation density, with the α volume fraction, consistent with strain-induced martensite α formation. Knowledge of the sample volume with the ε phase from the neutron diffraction analysis allowed us to identify the ε phase by electron back scatter diffraction analysis, complementing the neutron diffraction analysis with characterization on the grain level.
Isotope tracer studies, particularly radiocarbon measurements, play a key role in biological, nutritional, and environmental research. Accelerator mass spectrometry (AMS) is now the most sensitive detection method for 14C, but AMS is not widely used in kinetic studies of humans. Part of the reason is the expense, but costs would decrease if AMS were used more widely. One component in the cost is sample preparation for AMS. Biological and environmental samples are commonly reduced to graphite before they are analyzed by AMS. Improvements and mechanization of this multistep procedure is slowed by a lack of organized educational materials for AMS sample preparation that would allow new investigators to work with the technique without a substantial outlay of time and effort. We present a detailed sample preparation protocol for graphitizing biological samples for AMS and include examples of nutrition studies that have used this procedure.
The connection between the bi-polar hafnia-based resistive-RAM (RRAM) operational characteristics and dielectric structural properties is considered. Specifically, the atomic-level description of RRAM, which operations involve the repeatable rupture/recreation of a localized conductive path, reveals that its performance is determined by the outcome of the initial forming process defining the structural characteristics of the conductive filament and distribution of the oxygen ions released from the filament region. The post-forming ions spatial distribution in the cell is found to be linked to a degree of dielectric oxygen deficiency, which may either assist or suppress the resistive switching processes.
NASA's NuSTAR observatory is the first focusing hard X-ray telescope. Launched in June 2012, NuSTAR is sensitive in the 3–79 keV range with unprecedented ~17″ FWHM angular resolution above 12 keV, a result of its multilayer-coated optics and 10-m focal length. With its large effective area (900 cm2 at 10 keV), NuSTAR has point-source sensitivity ~100 times better than previous hard X-ray telescopes. Here we describe NuSTAR and its planned work on rotation-powered pulsars and magnetars during its nominal 2-yr baseline mission that has just commenced.
Background: The study investigated the change in proxy rated quality of life (QoL) of a large cohort of home living patients with Alzheimer's disease (AD) over a period of 36 months.
Methods: The sample consisted of 102 patients with mild AD and their primary caregivers from the Danish Alzheimer's Disease Intervention Study. QoL was assessed with the proxy-rated (primary caregivers) Quality of Life in Alzheimer Disease scale (QOL-AD) and the EuroQuol Visual Analogue Scale (EQ-VAS) scale. The Cornell Scale for Depression in Dementia (CSDD), Alzheimer's Disease Cooperative Study, Activities of Daily living Inventory (ADCS-ADL), Mini-Mental State Examination (MMSE) and Neuropsychiatric Inventory (NPI-Q) were also applied. Evaluations were conducted at baseline and at 12 and 36 months follow-up.
Results: There was a significant decline in mean QoL assessed by both the QOL-AD and the EQ-VAS (p < 0.001). There were vast individual differences in the QoL scores on both scales at 12 and 36 months’ follow-up. Mean change from baseline in QOL-AD was significantly associated with change in CSDD, ADCS-ADL and MMSE scores at 12 months and with ADCS-ADL score at 36 months.
Conclusion: QoL is a subjective concept and may not be influenced by the degree of cognitive dysfunction. Future studies should investigate the factors for individual variations in order to understand the nature of change of QoL in AD and the wide variation in QoL scores over time.
Hollow tubular structures of tyrocidines, a cyclic decapeptide with two amino acids residues in the D-configuration and eight in the L-configuration, were formed in acid aqueous solutions in the presence of ethanol (20°C). Discrete nanotubes can be produced under controlled conditions, e.g. the amount of water added, or in the presence of protons from ethanol-water solutions (45/55 %v/v). These cyclic oligopeptides crystallize into tubular structures hundreds of nanometer long with an internal diameter of 9.0 Å and outer diameter of 35 Å. Support for the proposed tubular structure is provided by electronmicroscopy, SAXS and Fourier-transform infrared spectroscopy. These structures are open-ended, having a uniform shape and constant internal diameter.
An equimolar mixture of palmitic acid (PA) and 1-lyso-palmitoyl-phosphatidylcholine (Lyso-PPC) has been studied by time-resolved small angle and wide angle X-ray scattering during temperature cycles between room temperature and 53.5 °C. In addition to the X-ray experiments, differential scanning calorimetry (DSC) with a similar temperature vs. time course was performed. At room temperature we observe a coexistence of two different lamellar phases. Our results indicate that in one of these lamellar phases, Lyso-PPC and PA associate in lamellar structures resembling di-palmitoyl-phosphatidylcholine (DPPC) bilayers, whereas the other phase is an interdigitated lamellar phase, where the acyl chains of both Lyso-PPC and PA extend across the entire hydrocarbon width of the bilayer. Upon heating, the latter phase disappears at 42 °C, corresponding to the chain-melting temperature for DPPC bilayers. At a higher temperature the remaining lamellar phase undergoes a phase transition into an isotropic micellar phase. In the cooling scans a particular slow kinetics of the regeneration of the two lamellar phases is observed. Our experiments provide new information about this system where only the DPPC-like mesophase has been reported before.
Extrusion freeform fabrication is a 3-D layerwise writing technique for forming objects directly under the control of a CAD program. This method is one of a family of rapid prototyping methods which include stereolithography, selective laser sintering and fused deposition modeling. This system can be used to build shapes, layer by layer, from hydrogels of agarose, polyacrylamide or other cross-linked water-soluble acrylic polymers.
Mineralization can be induced in these gels by building a part with alternating layers of gels containing calcium and carbonate or phosphate that can be formed into stacks which then mineralize by cross-diffusion. The write head can be conceived of as a cell which delivers the appropriate minerals to a site within a swollen gel matrix. This diffusive mineralization process can thus be compared with bone mineralization. The gel structure controls the morphology of the mineral. The site of mineralization is controlled by osmotic forces which localize most of the mineral in whichever zone has the higher ionic strength. The mineral content, expressed as a fraction of the polymer content, is similar to that of bone but the water content is much higher than in bone. This raises the question of what process drives the water exclusion during bone mineralization.
Through the use of solubilizing agents, simple salt metathesis reactions may be translated from aqueous solution to the milieu of organic solvents. When applied to the crystallization of calcium carbonate through the reaction of calcium chloride with sodium bicarbonate in “complexation-mediated” crystallization leads to the selective formation of a metastable phase, vaterite, rather than to calcite, the phase obtained from aqueous solution. Impacts on the formation of the third anhydrous phase of calcium carbonate, aragonite, are also noted. These studies suggest an additional mechanism whereby Nature may control the morphology and phase of the calcium carbonate biominerals.
We report here the first observation and microscopic characterization of tactoidal granules of actin in concentrated gels of actin filaments (F-actin). Phase contrast microscopy shows these stable tactoids of densely packed F-actin to be of various sizes on the order of 10 μm. The background gel of F-actin is optically birefringent, indicating orientational order of the filaments consistent with theoretical predictions. In contrast, no birefringence is detected through the tactoids, suggesting very distinct yet undetermined packing of the filaments inside. The tactoids demonstrate elastic response upon micromanipulation. The microscopic segregation of F-actin into two states of different protein concentrations is consistent with a first order phase transition between a nematic gel of lower concentration on the order of ten mg/nl and a highly packed, possibly columnar state of protein filaments. In addition to the excluded volume effects which are known to drive thermodynamic phase transitions as a function of particle concentration, additional molecular forces must also play important roles since the formation was found to be irreversible upon dilution.
We investigate the statistical mechanics of a torsionally constrained polymer. The polymer is modelled as an inextensible chain with bend rigidity A, twist rigidity C, and twist-stretch coupling D. In such a model, thermal bend fluctuations couple geometrically to an applied torque through the relation Lk = Tw + Wr. We explore this coupling and find excellent agreement between the predictions of our model and the single λ-DNA molecule stretching experiments of Strick et al. [Science 271 (1996) 1835]. This analysis affords an experimental determination of the microscopic twist rigidity C. Quantitative agreement between theory and experiment is obtained using C = 120 nm and D = 50 nm. The theory further predicts a thermal reduction of the effective twist rigidity induced by bend fluctuations.
Single and multicomponent membrane-mimetic surfaces of DPPC and synthetic lipid-peptide conjugates were formed on an alkylated glass surface by a process of vesicle fusion. Correlative atomic force microscopy and radiochemical titration techniques confirmed the generation of a single substrate supported monolayer and predictable deposition of defined concentrations of lipopeptide. Mixed systems were stable for periods exceeding 1 month if stored at room temperature in phosphate buffered saline.
We discuss a dynamical model for the frequency-dependent shear modulus of an entangled solution of semifexible polymers, based on longitudinal fluctuations in filaments between entanglement points or crosslinks. The goal is to explain non-Rouse, power-law scaling of the bulk shear modulus that is found via microscopic rheology of highly entangled F-actin solutions. This generalizes a previous model for the static modulus. Hydrodynamic effects, and the validity of a local drag approximation below the scale of the mesh size, are discussed. We test aspects of our model via a molecular dynamics simulation, and also present for comparison experimental results from microrheology on F-actin.
Poly[bis(trifluoroethoxy)phosphazene] (PTFEP) with a high purity and high molar mass is a biocompatible material  used as bulk material in medical implants. We developed a process to coat surfaces with PTFEP films and performed ELISA experiments designed to understand their blood compatibility. We observed that PTFEP adsorbs preferentially albumin from plasma, and only small amounts of coagulation or inflammation stimulating proteins. In general, there is a good correlation between increasing content of albumin in the adsorbed protein film and reduced platelet adhesion. Another important prerequisite of blood compatibility is the stabilization of the native state of adsorbed proteins, since denaturated proteins stimulate platelet adhesion. The elutability of adsorbed proteins by sodiumdodecylsulfate solution was used to quantify the amount of irreversible attached and presumably denaturated proteins. PTFEP showed a low amount of irreversibly adsorbed proteins of the coagulation cascade. Circular dichroism measurements of adsorbed fibrinogen and albumin showed only weak distortions of the secondary structure of these proteins on the surface of PTFEP.
We conclude that PTFEP has a unique blood compatibility because of the favorable composition and the stabilization of the protein layer against denaturation.
The yeast S. cereviseae represents the first eukaryotic organism whose genome has been entirely sequenced as a result of the Human Genome Project(1). In this report we demonstrate the good agreement between an experimental high resolution melting curve of total nuclear S. cereviseae DNA and the theoretical melting calculated for the complete yeast DNA genome (12,067,277 bp: Saccharomyces Genome Database) by the statistical thermodynamics program MELTSIM, parameterized for long DNA sequences(2,3). The experimental and theoretical melting curves are both fairly symmetrical and possess nearly identical Tm values. Calculated melting of coding and flanking DNA regions indicates that flanking DNAs are more (A+T)-rich than coding sequences and account for the earliest melting DNA. Calculated melting curves of the 16 individual yeast chromosomes are very similar and with few exceptions exhibit symmetric melting curves. MELTSIM was also used to calculate a theoretical denaturation map of Chromosome III DNA. The agreement between MELTSIM calculated and experimental melting data demonstrates our ability to accurately simulate long DNA sequence melting in complex eukaryotic genomes, whose sequences are becoming increasingly available for study in public databases. This has important consequences for the understanding of sequence dependent energetic properties of DNA in their biological sequence context and also for their potential use in biomaterials applications.
The general Lifshitz theory of van der Waals interaction was used to formulate and compute energies between the nucleotides situated on the opposite ends of a broken DNA helix. Our calculation show that infrared and ultraviolet resonances in the dielectric functions of DNA and the intracellular liquid account for less then 10 percent of the forces of interaction, at a range of 5-15 angstroms, between nucleotides. Thus the fundamental contribution to the interaction is presented by the group of resonances with frequencies of X - ray range. It was shown that during the interaction between thymine - guanine, adenine - guanine and cytosine - guanine there exists a potential barrier which prevents DNA selfrepairing after a mutanous, over a distance of about 7 - 20 angstroms, at the room temperature and with reference to the viscosity factor for pure water. All the remaining pairs of nucleotides have no such barrier. In addition the barrier vanishes and DNA undergoes complete selfrepairing with the decreace in viscosity of intracellular medium.
Normal endothelial cells (ECs), lining the blood vessels, are influenced by their interaction with the underlying potentially piezoelectric extracellular matrix (ECM). That this interaction may affect the EC metabolic state and functions in vivo prompted us to study the subsequent response of cultured ECs on indium-tin oxide (ITO) glass electrodes subjected to 1 hr of constant DC surface potential ranging from -0.3 to +0.6 V (vs. Ag/AgCl). We measured, relative to controls, cellular viability, growth rate and changes in actin microfilament organization in ECs over a subsequent 6 days in culture. The growth rate of ECs was stimulated by negative potential and inhibited by positive potential. Differences could be detected as early as three days post-potential. We also observed a potential dependent cellular shape change and actin microfilament rearrangement at positive potentials within four days of treatment. ECs changed in average cell surface area and assumed a polygonal cell shape in response to treatment. Using NBD-phalloidin stain for actin and fluorescence microscopy, microfilaments were observed to re-distribute to the periphery of the cell at positive potential, indicative of cellular stress.