Almost 50 million people worldwide are affected by Alzheimer’s disease (AD), the most common neurodegenerative disorder. Development of disease-modifying therapies would benefit from reliable, ...non-invasive positron emission tomography (PET) biomarkers for early diagnosis, monitoring of disease progression, and assessment of therapeutic effects. Traditionally, PET ligands have been based on small molecules that, with the right properties, can penetrate the blood–brain barrier (BBB) and visualize targets in the brain. Recently a new class of PET ligands based on antibodies have emerged, mainly in applications related to cancer. While antibodies have advantages such as high specificity and affinity, their passage across the BBB is limited. Thus, to be used as brain PET ligands, antibodies need to be modified for active transport into the brain. Here, we review the development of radioligands based on antibodies for visualization of intrabrain targets. We focus on antibodies modified into a bispecific format, with the capacity to undergo transferrin receptor 1 (TfR1)-mediated transcytosis to enter the brain and access pathological proteins, e.g. amyloid-beta. A number of such antibody ligands have been developed, displaying differences in brain uptake, pharmacokinetics, and ability to bind and visualize the target in the brain of transgenic mice. Potential pathological changes related to neurodegeneration, e.g. misfolded proteins and neuroinflammation, are suggested as future targets for this novel type of radioligand. Challenges are also discussed, such as the temporal match of radionuclide half-life with the ligand’s pharmacokinetic profile and translation to human use. In conclusion, brain PET imaging using bispecific antibodies, modified for receptor-mediated transcytosis across the BBB, is a promising method for specifically visualizing molecules in the brain that are difficult to target with traditional small molecule ligands.
We investigated magnesium ferrite MgFe2O4 nanoparticles synthesized by the sol-gel method followed by heat treatment at distinct temperatures. Specifically, we evaluated the influence of the heat ...treatment on the structural, magnetic, electrical, and dielectric properties of particles with dimensions of nm. Then, we brought a route, a synthesis method followed by heat treatment, that provide us the high control of the particle composition and particle size. X-ray diffraction analysis and transmission electron microscopy images revealed the formation of pure magnesium ferrite nanoparticles, with increasing average particle diameter with treatment temperature. The modifications of the structural parameters were correlated with the cation distribution between the tetrahedral (A) and octahedral B sites of the magnesium ferrite, which evolves with the increase of the Mg2+ ions at the B site as the heat treatment temperature is raised. The changes in the structural features induced by heat treatment at distinct temperatures led to modifications in the magnetic and dielectric properties of the ferrites. Magnetic characterization disclosed a dependence of the magnetic parameters with the treatment temperature. On the electric features, a decrease in the electrical resistivity with the treatment temperature was found, a fact primarily due to the increase of the grain size and the cation distribution of Mg and Fe. Regarding the dielectric characteristics, we disclosed low values for the dielectric constant and dielectric loss factor for the whole range of frequencies (0.1 up to 1.5 GHz), despite the dependence with the heat-treatment temperature and evolution with probe frequency. Through Mössbauer experiments, we elucidated the conduction mechanisms in our MgFe2O4 ferrite. Our results demonstrate that the structural, magnetic, electrical, and dielectric properties of MgFe2O4 nanoparticles can be tuned by the synthesis method followed by heat treatment. All these features place the magnesium ferrite MgFe2O4 nanoparticles, synthesized by sol-gel followed by heat treatment at distinct temperatures, suitable for sensor elements in technological devices and microwave applications.
•Sol-gel method followed by heat treatment is an e_cient route for the synthesis of MgFe2O4 nanoparticles.•A route that provide us the high control of the particle composition and particle size.•Tuning the structural, magnetic, electrical and dielectric properties of MgFe2O4 nanoparticles.•MgFe2O4 nanoparticles suitable for sensor elements in technological devices and microwave applications.
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Vascular density varies significantly between brain regions and between healthy and diseased tissue. However, current methods are arduous and time consuming. Herein we present a rapid ...simple method to quantify vascular density in brain. Normal brain vasculature is seen with indocyanine green fluorescence within the image.
•Semi-automated methodology utilizes fluorescence microscopy to calculate vascular density within brain and brain tumors.•Novel methodology produces data comparable to previously hand counting pathology methods.•Vascular density is decreased in experimental brain metastases compared to a preclinical glioma model.
Measurement of vascular density has significant value in characterizing healthy and diseased tissue, particularly in brain where vascular density varies among regions. Further, an understanding of brain vessel size helps distinguish between capillaries and larger vessels like arterioles and venules. Unfortunately, few cutting edge methodologies are available to laboratories to rapidly quantify vessel density.
We developed a rapid microscopic method, which quantifies the numbers and diameters of blood vessels in brain. Utilizing this method we characterized vascular density of five brain regions in both mice and rats, in two tumor models, using three tracers.
We observed the number of sections/mm2 in various brain regions: genu of corpus callosum 161±7, hippocampus 266±18, superior colliculus 300±24, frontal cortex 391±55, and inferior colliculus 692±18 (n=5 animals). Regional brain data were not significantly different between species (p>0.05) or when using different tracers (70kDa and 2000kDa Texas Red; p>0.05). Vascular density decreased (62–79%) in preclinical brain metastases but increased (62%) a rat glioma model.
Our values were similar (p>0.05) to published literature. We applied this method to brain-tumors and observed brain metastases of breast cancer to have a ∼2.5-fold reduction (p>0.05) in vessels/mm2 compared to normal cortical regions. In contrast, vascular density in a glioma model was significantly higher (sections/mm2 736±84; p<0.05).
In summary, we present a vascular density counting method that is rapid, sensitive, and uses fluorescence microscopy without antibodies.
Background
Cryoballoon ablation (CBA) for paroxysmal atrial fibrillation (pAF) can be performed under general anesthesia (GA) or moderate sedation (MS). Our objective was to compare the ...effectiveness, safety, procedure duration, and time spent in the electrophysiology (EP) laboratory for CBA performed under GA and MS.
Methods
Patients undergoing a first CBA for pAF were identified. Patients received either GA administered by an anesthesiologist or MS with midazolam and fentanyl administered by EP laboratory staff. Total time in laboratory (sum of procedure and nonprocedure time); fluoroscopy time; freedom from documented AF, atrial flutter, and atrial tachycardia (FFAF); acute pulmonary vein isolation (PVI) rate; and 30‐day complication rate were assessed.
Results
A total of 55 patients received GA and 119 patients received MS. PVI success rate was 100% in GA and 98.1% in MS (P = 0.04). Total laboratory time was longer for GA (280.4 ± 54.1 minutes vs 245.5 ± 54.7 minutes; P < 0.001), related to longer nonprocedure time (92.2 ± 28.8 minutes GA vs 71.0 ± 30.0 minutes MS; P < 0.001), but not procedure time (188.3 ± 49.3 minutes GA vs 174.5 ± 50.2 minutes MS; P = 0.09). FFAF was not significantly different over a median follow‐up duration of 0.9 (interquartile range 0.4–1.9) years (61.8% GA vs 63.0% MS; log‐rank P = 0.90). There was no significant difference in complication rate.
Conclusion
Compared to GA, MS during CBA for pAF was independently associated with shorter total EP laboratory time without compromising FFAF or complication rates.
Anadromous Arctic charr
Salvelinus alpinus
is a cold-adapted salmonid that is vulnerable to climate warming and anthropogenic activities including salmon farming, hydropower regulation, and ...pollution, which poses a multiple-stressor scenario that influences or threatens populations. We studied the horizontal and vertical behaviour of Arctic charr tagged with acoustic transmitters (n = 45, mean fish length: 22 cm) in a pristine, subarctic marine area to provide insights into the behaviour of first-time migrants. Tagged fish spent up to 78 d at sea, with high marine survival (82% returned to their native watercourse). While at sea, they utilized mostly near-shore areas, up to 45 km away from their native river. Arctic charr showed large variation in migration distance (mean ± SD: 222 ± 174 km), and the migration distance increased with body size. Although the fish displayed a strong fidelity to surface waters (0-3 m), spatiotemporal variation in depth use was evident, with fish utilizing deeper depths during the day and in late July. These results represent baseline data on Arctic charr’s marine behaviour in a pristine fjord system and highlight the importance of near-shore surface water as feeding areas for first-time migrants. Furthermore, the observed dependency on coastal areas implies a vulnerability to increasing human-induced perturbations, on top of impacts by large-scale climate change in marine and freshwater habitats.
Abstract
We have modeled the velocity-resolved reverberation response of the H
β
broad emission line in nine Seyfert 1 galaxies from the Lick Active Galactic Nucleus (AGN) Monitoring Project 2016 ...sample, drawing inferences on the geometry and structure of the low-ionization broad-line region (BLR) and the mass of the central supermassive black hole. Overall, we find that the H
β
BLR is generally a thick disk viewed at low to moderate inclination angles. We combine our sample with prior studies and investigate line-profile shape dependence, such as
log
10
(
FWHM
/
σ
)
, on BLR structure and kinematics and search for any BLR luminosity-dependent trends. We find marginal evidence for an anticorrelation between the profile shape of the broad H
β
emission line and the Eddington ratio, when using the rms spectrum. However, we do not find any luminosity-dependent trends, and conclude that AGNs have diverse BLR structure and kinematics, consistent with the hypothesis of transient AGN/BLR conditions rather than systematic trends.
Over the last 70 yr, more than 12,000 maize accessions have been screened for their level of resistance to western corn rootworm, Diabrotica virgifera virgifera (LeConte; Coleoptera: Chrysomelidae), ...larval feeding. Less than 1% of this germplasm was selected for initiating recurrent selection or other breeding programs. Selected genotypes were mostly characterized by large root systems and superior root regrowth after root damage caused by western corn rootworm larvae. However, no hybrids claiming native (i.e., host plant) resistance to western corn rootworm larval feeding are currently commercially available. We investigated the genetic basis of western corn rootworm resistance in maize materials with improved levels of resistance using linkage disequilibrium mapping approaches. Two populations of topcrossed doubled haploid maize lines (DHLs) derived from crosses between resistant and susceptible maize lines were evaluated for their level of resistance in three to four different environments. For each DHL topcross an average root damage score was estimated and used for quantitative trait loci (QTL) analysis. We found genomic regions contributing to western corn rootworm resistance on all maize chromosomes, except for chromosome 4. Models fitting all QTL simultaneously explained about 30 to 50% of the genotypic variance for root damage scores in both mapping populations. Our findings confirm the complex genetic structure of host plant resistance against western corn rootworm larval feeding in maize. Interestingly, three of these QTL regions also carry genes involved in ascorbate biosynthesis, a key compound we hypothesize is involved in the expression of western corn rootworm resistance.
Preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2_ infections in healthcare workers (HCWs) is critical for healthcare delivery. We aimed to estimate and characterize the ...prevalence and incidence of coronavirus disease 2019 (COVID-19) in a US HCW cohort and to identify risk factors associated with infection.
We conducted a longitudinal cohort study of HCWs at 3 Bay Area medical centers using serial surveys and SARS-CoV-2 viral and orthogonal serological testing, including measurement of neutralizing antibodies. We estimated baseline prevalence and cumulative incidence of COVID-19. We performed multivariable Cox proportional hazards models to estimate associations of baseline factors with incident infections and evaluated the impact of time-varying exposures on time to COVID-19 using marginal structural models.
A total of 2435 HCWs contributed 768 person-years of follow-up time. We identified 21 of 2435 individuals with prevalent infection, resulting in a baseline prevalence of 0.86% (95% confidence interval CI, .53%-1.32%). We identified 70 of 2414 incident infections (2.9%), yielding a cumulative incidence rate of 9.11 cases per 100 person-years (95% CI, 7.11-11.52). Community contact with a known COVID-19 case was most strongly correlated with increased hazard for infection (hazard ratio, 8.1 95% CI, 3.8-17.5). High-risk work-related exposures (ie, breach in protective measures) drove an association between work exposure and infection (hazard ratio, 2.5 95% CI, 1.3-4.8). More cases were identified in HCWs when community case rates were high.
We observed modest COVID-19 incidence despite consistent exposure at work. Community contact was strongly associated with infections, but contact at work was not unless accompanied by high-risk exposure.
Coastal defence structures are proliferating as a result of rising sea levels and stormier seas. With the realisation that most coastal infrastructure cannot be lost or removed, research is required ...into ways that coastal defence structures can be built to meet engineering requirements, whilst also providing relevant ecosystem services—so-called ecological engineering. This approach requires an understanding of the types of assemblages and their functional roles that are desirable and feasible in these novel ecosystems. We review the major impacts coastal defence structures have on surrounding environments and recent experiments informing building coastal defences in a more ecologically sustainable manner. We summarise research carried out during the THESEUS project (2009–2014) which optimised the design of coastal defence structures with the aim to conserve or restore native species diversity. Native biodiversity could be manipulated on defence structures through various interventions: we created artificial rock pools, pits and crevices on breakwaters; we deployed a precast habitat enhancement unit in a coastal defence scheme; we tested the use of a mixture of stone sizes in gabion baskets; and we gardened native habitat-forming species, such as threatened canopy-forming algae on coastal defence structures. Finally, we outline guidelines and recommendations to provide multiple ecosystem services while maintaining engineering efficacy. This work demonstrated that simple enhancement methods can be cost-effective measures to manage local biodiversity. Care is required, however, in the wholesale implementation of these recommendations without full consideration of the desired effects and overall management goals.
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