The generation and function of soluble apoE receptors in the CNS

More than a decade has passed since apolipoprotein E4 (APOE-ε4) was identified as a primary risk factor for Alzheimer 's disease (AD), yet researchers are even now struggling to understand how the apolipoprotein system integrates into the puzzle of AD etiology. The specific pathological actions of apoE4, methods of modulating apolipoprotein E4-associated risk, and possible roles of apoE in normal synaptic function are still being debated. These critical questions will never be fully answered without a complete understanding of the life cycle of the apolipoprotein receptors that mediate the uptake, signaling, and degradation of apoE. The present review will focus on apoE receptors as modulators of apoE actions and, in particular, explore the functions of soluble apoE receptors, a field almost entirely overlooked until now

Soluble apoE/Aβ complex: mechanism and therapeutic target for APOE4-induced AD risk

The APOE4 allele of apolipoprotein E (apoE) is the greatest genetic risk factor for Alzheimer\u27s disease (AD) compared to APOE2 and APOE3. Amyloid-β (Aβ), particularly in a soluble oligomeric form (oAβ), is considered a proximal cause of neurodegeneration in AD. Emerging data indicate that levels of soluble oAβ are increased with APOE4, providing a potential mechanism of APOE4-induced AD risk. However, the pathway(s) by which apoE4 may increase oAβ levels are unclear and the subject of continued inquiry. In this editorial review, we present the hypothesis that apoE isoform-specific interactions with Aβ, namely apoE/Aβ complex, modulate Aβ levels. Specifically, we propose that compared to apoE3, apoE4-containing lipoproteins are less lipidated, leading to less stable apoE4/Aβ complexes, resulting in reduced apoE4/Aβ levels and increased accumulation, particularly of oAβ. Evidence that support or counter this argument, as well as the therapeutic significance of this pathway to neurodegeneration, are discussed

IC 485:a new candidate disk-maser galaxy at ∼\sim100 Mpc distance. Milliarcsecond resolution study of the galaxy nucleus and of the H2OH_{2}O megamaser

Masers are a unique tool to investigate the emitting gas in the innermost regions of AGNs and to map accretion disks and tori orbiting around supermassive black holes. IC485, which is classified as a LINER or Seyfert galaxy, hosts a bright water maser whose nature is still under debate. Indeed, this might be either a nuclear disk maser, a jet/outflow maser, or even the very first `inclined water maser disk'. We aim to investigate the nature of the maser by determining the location and the distribution of the maser emission at mas resolution and by associating it with the main nuclear components of IC485. In a broader context, this work might also provide further information for better understanding the physics and the disk/jet geometry in LINER or Seyfert galaxies. We observed in 2018 the nuclear region of IC485 in continuum and spectral-line mode with the VLBA and the EVN at L, C, and K bands (linear scales from ~3 to 0.2 pc). We detected 2 water maser components separated in velocity by 472 km/s, with one centred at the systemic velocity of the nuclear region and the other at a red-shifted velocity. We measured for the first time the absolute positions of these components with an accuracy of ~0.1 mas. Assuming a maser associated with an edge-on disk in Keplerian rotation, the estimated enclosed mass is M_BH = 1.2 x 10^7 M_sun, consistent with the expected mass for a SMBH in a LINER or Seyfert galaxy. The linear distribution of the maser components and a comparison with the high sensitivity GBT spectrum strongly suggest that the bulk of the maser emission is associated with an edge-on accretion disk. This makes IC485 a new candidate for a disk-maser galaxy at the distance of 122 Mpc. In particular, thanks to the upcoming radio facilities (e.g., the SKA and the ngVLA) IC485 will play an important role in our understanding of AGNs in an unexplored volume of Universe.Comment: 13 pages, 10 figures, 6 tables, accepted by Astronomy & Astrophysic

Soluble apoE/Aβ Complex: Mechanism and Therapeutic target for APOE4-induced AD Risk

The APOE4 allele of apolipoprotein E (apoE) is the greatest genetic risk factor for Alzheimer\u27s disease (AD) compared to APOE2 and APOE3. Amyloid-β (Aβ), particularly in a soluble oligomeric form (oAβ), is considered a proximal cause of neurodegeneration in AD. Emerging data indicate that levels of soluble oAβ are increased with APOE4, providing a potential mechanism of APOE4-induced AD risk. However, the pathway(s) by which apoE4 may increase oAβ levels are unclear and the subject of continued inquiry. In this editorial review, we present the hypothesis that apoE isoform-specific interactions with Aβ, namely apoE/Aβ complex, modulate Aβ levels. Specifically, we propose that compared to apoE3, apoE4-containing lipoproteins are less lipidated, leading to less stable apoE4/Aβ complexes, resulting in reduced apoE4/Aβ levels and increased accumulation, particularly of oAβ. Evidence that support or counter this argument, as well as the therapeutic significance of this pathway to neurodegeneration, are discussed

Optical design of S-band multifeed for the Sardinia Radio Telescope primary focus

We present the optical design of an S-band seven feed cryogenic radio astronomy receiver for illuminating the 64-m diameter Sardinia Radio Telescope (SRT) dish from the primary focus. The feeds are arranged in a compact hexagonal configuration with a central one and are cryogenically cooled at 20 K inside a cryostat. Each feed accepts two linear polarizations and use a circular waveguide with a single outer corrugated section to achieve a nearly constant beamwidth and low cross polarization across the 3.0-4.5 GHz band. The simulated radiation pattern of the SRT telescope is obtained by coupling the array of feed-horn beam patterns (optimized with the electromagnetic software CST) with the 64-m parabolic dish (through a physical optics analysis carried out with GRASP). We compare the simulated beam pattern of an isolated feed with those of the same feed embedded in the dense array and analyze the effects of an absorber located inside the cryostat around the cryogenic feeds. We found that the absorber improves the overall system performance by decreasing the cross-coupling effects between the feeds while adding negligible noise to the system

Imaging of SNR IC443 and W44 with the Sardinia Radio Telescope at 1.5 GHz and 7 GHz

Observations of supernova remnants (SNRs) are a powerful tool for investigating the later stages of stellar evolution, the properties of the ambient interstellar medium, and the physics of particle acceleration and shocks. For a fraction of SNRs, multi-wavelength coverage from radio to ultra high-energies has been provided, constraining their contributions to the production of Galactic cosmic rays. Although radio emission is the most common identifier of SNRs and a prime probe for refining models, high-resolution images at frequencies above 5 GHz are surprisingly lacking, even for bright and well-known SNRs such as IC443 and W44. In the frameworks of the Astronomical Validation and Early Science Program with the 64-m single-dish Sardinia Radio Telescope, we provided, for the first time, single-dish deep imaging at 7 GHz of the IC443 and W44 complexes coupled with spatially-resolved spectra in the 1.5-7 GHz frequency range. Our images were obtained through on-the-fly mapping techniques, providing antenna beam oversampling and resulting in accurate continuum flux density measurements. The integrated flux densities associated with IC443 are S_1.5GHz = 134 +/- 4 Jy and S_7GHz = 67 +/- 3 Jy. For W44, we measured total flux densities of S_1.5GHz = 214 +/- 6 Jy and S_7GHz = 94 +/- 4 Jy. Spectral index maps provide evidence of a wide physical parameter scatter among different SNR regions: a flat spectrum is observed from the brightest SNR regions at the shock, while steeper spectral indices (up to 0.7) are observed in fainter cooling regions, disentangling in this way different populations and spectra of radio/gamma-ray-emitting electrons in these SNRs.Comment: 13 pages, 9 figures, accepted for publication to MNRAS on 18 May 201

Genetics Ignite Focus on Microglial Inflammation in Alzheimer\u27s Disease

In the past five years, a series of large-scale genetic studies have revealed novel risk factors for Alzheimer\u27s disease (AD). Analyses of these risk factors have focused attention upon the role of immune processes in AD, specifically microglial function. In this review, we discuss interpretation of genetic studies. We then focus upon six genes implicated by AD genetics that impact microglial function: TREM2, CD33, CR1, ABCA7, SHIP1, and APOE. We review the literature regarding the biological functions of these six proteins and their putative role in AD pathogenesis. We then present a model for how these factors may interact to modulate microglial function in AD

Sardinia Radio Telescope wide-band spectral-polarimetric observations of the galaxy cluster 3C 129

We present new observations of the galaxy cluster 3C 129 obtained with the Sardinia Radio Telescope in the frequency range 6000-7200 MHz, with the aim to image the large-angular-scale emission at high-frequency of the radio sources located in this cluster of galaxies. The data were acquired using the recently-commissioned ROACH2-based backend to produce full-Stokes image cubes of an area of 1 deg x 1 deg centered on the radio source 3C 129. We modeled and deconvolved the telescope beam pattern from the data. We also measured the instrumental polarization beam patterns to correct the polarization images for off-axis instrumental polarization. Total intensity images at an angular resolution of 2.9 arcmin were obtained for the tailed radio galaxy 3C 129 and for 13 more sources in the field, including 3C 129.1 at the galaxy cluster center. These data were used, in combination with literature data at lower frequencies, to derive the variation of the synchrotron spectrum of 3C 129 along the tail of the radio source. If the magnetic field is at the equipartition value, we showed that the lifetimes of radiating electrons result in a radiative age for 3C 129 of t_syn = 267 +/- 26 Myrs. Assuming a linear projected length of 488 kpc for the tail, we deduced that 3C 129 is moving supersonically with a Mach number of M=v_gal/c_s=1.47. Linearly polarized emission was clearly detected for both 3C 129 and 3C 129.1. The linear polarization measured for 3C 129 reaches levels as high as 70% in the faintest region of the source where the magnetic field is aligned with the direction of the tail.Comment: 19 pages, 17 figures, accepted for publication in MNRA

Ultrasonographic assessment of spleen size and pattern of change among sickle cell disease patients and healthy controls in North-Eastern Nigeria

Background: Ultrasonography is an established and reliable method for assessing the spleen. Because of variation due to genetic and other environmental factors including malaria endemicity, interpretation of spleen sizes requires a knowledge of the normal reference range for a given population. This study aimed to identify spleen size reference ranges across age groups of healthy controls to serve as a baseline to assess changes in spleen size in patients with sickle cell disease. Methods: Using a cross-sectional study design, spleen size was measured in healthy people of different age groups and steady-state sickle cell disease patients (children and adults) using abdominal ultrasonography. Using the age-group-specific reference values obtained from the controls, spleens were classified into small, normal size or enlarged among the sickle cell disease patients. Results: The study consisted of 109 (34.8%) healthy controls and 204 (65.2%) steady-state sickle cell disease patients. The spleen was visualised in all the controls ( n = 109) and in 107 (52.4%) sickle cell disease patients. Using cut-off values for spleen length among the controls across age groups (< 5 years (5.0–7.0 cm); 5–9 years (5.5–8.5 cm); 10–14 years (6.0–11.0 cm) and ⩾ 15 years (7.0–12.5 cm)), spleen size was classified as small ( n = 18/204; 8.87%), normal ( n = 68/204; 33.3%) and enlarged ( n = 21/204; 10.3%) among the sickle cell disease patients. Conclusion: Model-based age-group reference ranges and percentile curves for splenic dimensions based on ultrasonography among normal controls in North-Eastern Nigeria were established and may be of value in assessing spleen sizes among sickle cell disease patients living in malaria-endemic regions of Africa

Determinants of splenic preservation among patients with sickle cell disease in North‐Eastern Nigeria

Objective: In patients with sickle cell disease (SCD), the spleen commonly enlarges during early childhood, but undergoes reduction in size and fibrosis from repeated episodes of vaso‐occlusion and infarction. The rate of progression of this process varies markedly among these patients. The aim of current study was to explore clinical and laboratory factors associated with the preservation of the spleen among these patients. Methods: Two hundred four patients with SCD (103 females; age 1–45 years) underwent abdominal ultrasonography at the University of Maiduguri Teaching Hospital, Nigeria between October 2020 and November 2021 to assess for splenic visualisation and echotexture. Steady‐state clinical parameters and blood samples for full blood count, serum chemistry, high‐performance liquid chromatography and malaria parasitemia were obtained from all the patients. Results: The spleen was visualised in 107 (52.4%; 95% confidence interval [CI], 46%–59%) patients with SCD on ultrasonography. While the spleen was visualised in all children less than 5 years of age, it was visualised in only 23.5% of those aged 15 years and older. Visualisation of the spleen was significantly associated with low mean corpuscular haemoglobin concentration and high haemoglobin F (HbF) in those younger than 10 years. The odds of visualisation of the spleen on ultrasonography increased by a factor of 1.17% for every 1% increase in HbF level. Only 32 (15%) patients were on regular hydroxyurea therapy. The HbF level was significantly higher among patients on hydroxyurea (median 12.7 vs. 7.4; p < 0.0001). Conclusion: In patients with SCD, failure to visualise the spleen was not found in children less than 5 years old. Patients with visualised spleens had a higher level of HbF than those with non‐visualised spleens. HbF was significantly associated with visualisation of the spleen before 10 years of age. Since early administration of hydroxyurea will increase HbF level, we expect that it would help to preserve the spleen