Abstract Although hypertension has been implicated in the pathogenesis of vascular disease, its role in inflammatory responses, especially in brain, remains unclear. In this study we found key ...mechanisms by which angiotensin II (AngII) mediates cerebral microvascular inflammation. C57BL/6 male mice were subjected to slow-pressor dose of AngII infusion using osmotic mini-pumps at a rate of 400 ng/kg/min for 14 days. Vascular inflammation in the brain was evaluated by analysis of leukocyte–endothelial interaction and blood–brain barrier (BBB) permeability. Results from intravital microscopy of pial vessels in vivo , revealed a 4.2 fold ( P <0.05, compared to vehicle) increase in leukocyte adhesion on day 4 of AngII infusion. This effect persisted through day 14 of AngII infusion, which resulted in a 2.6 fold ( P <0.01, compared to vehicle) increase in leukocyte adhesion. Furthermore, evaluation of BBB permeability by Evans Blue extravasation showed that Ang II significantly affected the BBB, inducing 3.8 times ( P <0.05, compared to vehicle) higher permeability. Previously we reported that AngII mediated hypertension promotes oxidative stress in the vasculature. Thus, we used the superoxide scavenger; 4-hydroxy-TEMPO (Tempol) to determine whether AngII via oxidative stress could contribute to higher leukocyte adhesion and increased BBB permeability. Tempol was given via drinking water (2 mmol) on day 4th following Ang II infusion, since oxidative stress increases in this model on day 4. Treatment with Tempol significantly attenuated the increased leukocyte/endothelial interactions and protected the BBB integrity on day 14 of AngII infusion. In conclusion, AngII via oxidative stress increases cerebral microvasculature inflammation and leads to greater immune-endothelial interaction and higher BBB permeability. This finding may open new avenues for the management of nervous system pathology involving cerebrovascular inflammation.
Anthropogenic litter is present in all marine habitats, from beaches to the most remote points in the oceans. On the seafloor, marine litter, particularly plastic, can accumulate in high densities ...with deleterious consequences for its inhabitants. Yet, because of the high cost involved with sampling the seafloor, no large-scale assessment of distribution patterns was available to date. Here, we present data on litter distribution and density collected during 588 video and trawl surveys across 32 sites in European waters. We found litter to be present in the deepest areas and at locations as remote from land as the Charlie-Gibbs Fracture Zone across the Mid-Atlantic Ridge. The highest litter density occurs in submarine canyons, whilst the lowest density can be found on continental shelves and on ocean ridges. Plastic was the most prevalent litter item found on the seafloor. Litter from fishing activities (derelict fishing lines and nets) was particularly common on seamounts, banks, mounds and ocean ridges. Our results highlight the extent of the problem and the need for action to prevent increasing accumulation of litter in marine environments.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Adeno-associated virus (AAV) vectors are showing promise in gene therapy trials and have proven to be extremely efficient biological tools in basic neuroscience research. One major limitation to ...their widespread use in the neuroscience laboratory is the cost, labor, skill and time-intense purification process of AAV. We have recently shown that AAV can associate with exosomes (exo-AAV) when the vector is isolated from conditioned media of producer cells, and the exo-AAV is more resistant to neutralizing anti-AAV antibodies compared with standard AAV. Here, we demonstrate that simple pelleting of exo-AAV from media via ultracentrifugation results in high-titer vector preparations capable of efficient transduction of central nervous system (CNS) cells after systemic injection in mice. We observed that exo-AAV is more efficient at gene delivery to the brain at low vector doses relative to conventional AAV, even when derived from a serotype that does not normally efficiently cross the blood-brain barrier. Similar cell types were transduced by exo-AAV and conventionally purified vector. Importantly, no cellular toxicity was noted in exo-AAV-transduced cells. We demonstrated the utility and robustness of exo-AAV-mediated gene delivery by detecting direct GFP fluorescence after systemic injection, allowing three-dimensional reconstruction of transduced Purkinje cells in the cerebellum using ex vivo serial two-photon tomography. The ease of isolation combined with the high efficiency of transgene expression in the CNS, may enable the widespread use of exo-AAV as a neuroscience research tool. Furthermore, the ability of exo-AAV to evade neutralizing antibodies while still transducing CNS after peripheral delivery is clinically relevant.
ABSTRACT
We present a second paper related to the analyses of high-dispersion spectroscopic observations of the magnetic cataclysmic variable AE Aquarii. We focus our efforts on the study of the ...emission lines and their radial velocities. We detect a sinusoidal behaviour, in several of the observing runs, with variable amplitudes. Of those runs presented, the velocity curve of 2000 August shows less instability in the emission material. In this case, we obtain K1 = 114 ± 8 km s−1, which we take as our best value for the radial velocity of the primary. This result is consistent within 2σ with previously published values obtained using indirect methods. We interpret this consistency as observational evidence of material orbiting the rapidly rotating primary star. We present a Doppler tomography study, which shows that the H α emission is primarily concentrated within a blob in the lower left quadrant, a structure similar to that predicted by the propeller model. However, for 2000 August, we find the emission centred around the position of the white dwarf, which supports the possibility of the K1 value of this run of being a valid approximation of the orbital motion of the white dwarf.
Background
Season of birth influences allergy risk; however, the biological mechanisms underlying this observation are unclear. The environment affects DNA methylation, with potentially long‐lasting ...effects on gene expression and disease. This study examined whether DNA methylation could underlie the association between season of birth and allergy.
Methods
In a subset of 18‐year‐old participants from the Isle of Wight (IoW) birth cohort (n = 367), the risks of birth season on allergic outcomes were estimated. Whole blood epigenome‐wide DNA methylation was measured, and season‐associated CpGs detected using a training‐and‐testing‐based technique. Validation method examined the 8‐year‐old Prevention and Incidence of Asthma and Mite Allergy (PIAMA) cohort. The relationships between DNA methylation, season of birth and allergy were examined. CpGs were analysed in IoW third‐generation cohort newborns.
Results
Autumn birth increased risk of eczema, relative to spring birth. Methylation at 92 CpGs showed association with season of birth in the epigenome‐wide association study. In validation, significantly more CpGs had the same directionality than expected by chance, and four were statistically significant. Season‐associated methylation was enriched among networks relating to development, the cell cycle and apoptosis. Twenty CpGs were nominally associated with allergic outcomes. Two CpGs were marginally on the causal pathway to allergy. Season‐associated methylation was largely absent in newborns, suggesting it arises post‐natally.
Conclusions
This study demonstrates that DNA methylation in adulthood is associated with season of birth, supporting the hypothesis that DNA methylation could mechanistically underlie the effect of season of birth on allergy, although other mechanisms are also likely to be involved.
Lactobacillus casei was entrapped in beads made with sodium alginate (A), amidated low-methoxyl pectin (P), and blends of A–P (1:2, 1:4, 1:6 ratios) by the extrusion technique. Diameter, sphericity ...and textural properties of the beads and the survivability of entrapped
Lb. casei in yoghurt and in simulated gastrointestinal conditions were determined. Entrapment efficiency of
Lb. casei and diameter increased as the proportion of P and the total biopolymers concentration increased. Principal Component Analysis showed that the survivability of
Lb. casei in yoghurt, and in simulated gastric juice, was positively correlated with the diameter and all the textural properties of the beads, while survivability after exposure to simulated gastric juice and bile salts was positively correlated with the sphericity of the beads. The beads made with A–P blends in 1:4 and 1:6 ratios provided a significant better protection to the entrapped
Lb. casei under all conditions studied.
ABSTRACT
We present extensive radial velocity observations of the intermediate polar DW Cnc during its 2018–2019 low state. We show that the 86 min signal associated with the orbital period is strong ...in our radial velocity analysis, power spectrum search, and in our Doppler tomography. However, we find that the velocity modulation associated with the 70 min beat period and the 38 min spin cycle is dramatically weaker than that previously observed. We put forward two interpretations for this change. The first is that a sudden drop into a low state detected in 2018–2019 caused an episode of low mass transfer from the companion, thus inhibiting the lighthouse effect produced by the rebound emission. The second is that this is a consequence of a rare outburst detected in 2007 by Crawford et al. (2008). We find this post-outburst hypothesis to be less likely. If the first scenario is correct, we predict that DW Cnc will recover its intermediate polar characteristics. A new ephemeris is presented by combining Patterson et al. (2004) radial velocities with ours.
ABSTRACT
We present a line-by-line differential analysis of a sample of 16 planet-hosting stars and 68 comparison stars using high-resolution, high signal-to-noise ratio spectra gathered using Keck. ...We obtained accurate stellar parameters and high-precision relative chemical abundances with average uncertainties in Teff, log g, Fe/H, and X/H of 15 K, 0.034 cm s−2
, 0.012 dex, and 0.025 dex, respectively. For each planet host, we identify a set of comparison stars and examine the abundance differences (corrected for Galactic chemical evolution effect) as a function of the dust condensation temperature, Tcond, of the individual elements. While we confirm that the Sun exhibits a negative trend between abundance and Tcond, we also confirm that the remaining planet hosts exhibit a variety of abundance–Tcond trends with no clear dependence upon age, metallicity, or Teff. The diversity in the chemical compositions of planet-hosting stars relative to their comparison stars could reflect the range of possible planet-induced effects present in these planet hosts, from the sequestration of rocky material (refractory poor) to the possible ingestion of planets (refractory rich). Other possible explanations include differences in the time-scale, efficiency and degree of planet formation, or inhomogeneous chemical evolution. Although we do not find an unambiguous chemical signature of planet formation among our sample, the high-precision chemical abundances of the host stars are essential for constraining the composition and structure of their exoplanets.
Analysis of single-molecule brightness allows subunit counting of high-order oligomeric biomolecular complexes. Although the theory behind the method has been extensively assessed, systematic ...analysis of the experimental conditions required to accurately quantify the stoichiometry of biological complexes remains challenging. In this work, we develop a high-throughput, automated computational pipeline for single-molecule brightness analysis that requires minimal human input. We use this strategy to systematically quantify the accuracy of counting under a wide range of experimental conditions in simulated ground-truth data and then validate its use on experimentally obtained data. Our approach defines a set of conditions under which subunit counting by brightness analysis is designed to work optimally and helps in establishing the experimental limits in quantifying the number of subunits in a complex of interest. Finally, we combine these features into a powerful, yet simple, software that can be easily used for the analysis of the stoichiometry of such complexes.
Background
WHO guidelines advocate breastfeeding for 6 months, and EAACI guideline recommends exclusive breastfeeding for 4–6 months. However, evidence for breastfeeding to prevent asthma and ...allergic disease is conflicting. We examined whether following recommended breastfeeding guidelines alters the long‐term risks of asthma, eczema, rhinitis or atopy.
Methods
The effect of nonexclusive (0, >0–6, >6 months) and exclusive breastfeeding (0, >0–4, >4 months) on repeated measures of asthma (10, 18 years), eczema, rhinitis, and atopy (1‐or‐2, 4, 10, 18 years) risks was estimated in the IoW cohort (n = 1456) using log‐linear models with generalized estimating equations. The Food Allergy and Intolerance Research (FAIR) cohort (n = 988), also from the IoW, was examined to replicate results.
Results
Breastfeeding (any or exclusive) had no effect on asthma and allergic disease in the IoW cohort. In the FAIR cohort, any breastfeeding for >0–6 months protected against asthma at 10 years (RR = 0.50, 95% CI = 0.32–0.79, P = 0.003), but not other outcomes, whilst exclusive breastfeeding for >4 months protected against repeated rhinitis (RR = 0.36, 95% CI = 0.18–0.71, P = 0.003). Longer breastfeeding was protective against late‐onset wheeze in the IoW cohort.
Conclusion
The protective effects of nonexclusive and exclusive breastfeeding against long‐term allergic outcomes were inconsistent between these colocated cohorts, agreeing with previous observations of heterogeneous effects. Although breastfeeding should be recommended for other health benefits, following breastfeeding guidelines did not appear to afford a consistent protection against long‐term asthma, eczema, rhinitis or atopy. Further research is needed into the long‐term effects of breastfeeding on allergic disease.
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