Controlled cortical impact traumatic brain injury in 3xTg-AD mice causes acute intra-axonal amyloid-β accumulation and independently accelerates the development of tau abnormalities

Alzheimer\u27s disease (AD) is a neurodegenerative disorder characterized pathologically by progressive neuronal loss, extracellular plaques containing the amyloid-β (Aβ) peptides, and neurofibrillary tangles composed of hyperphosphorylated tau proteins. Aβ is thought to act upstream of tau, affecting its phosphorylation and therefore aggregation state. One of the major risk factors for AD is traumatic brain injury (TBI). Acute intra-axonal Aβ and diffuse extracellular plaques occur in ∼30% of human subjects after severe TBI. Intra-axonal accumulations of tau but not tangle-like pathologies have also been found in these patients. Whether and how these acute accumulations contribute to subsequent AD development is not known, and the interaction between Aβ and tau in the setting of TBI has not been investigated. Here, we report that controlled cortical impact TBI in 3xTg-AD mice resulted in intra-axonal Aβ accumulations and increased phospho-tau immunoreactivity at 24 h and up to 7 d after TBI. Given these findings, we investigated the relationship between Aβ and tau pathologies after trauma in this model by systemic treatment of Compound E to inhibit γ-secretase activity, a proteolytic process required for Aβ production. Compound E treatment successfully blocked posttraumatic Aβ accumulation in these injured mice at both time points. However, tau pathology was not affected. Our data support a causal role for TBI in acceleration of AD-related pathologies and suggest that TBI may independently affect Aβ and tau abnormalities. Future studies will be required to assess the behavioral and long-term neurodegenerative consequences of these pathologies

Imaging of the Merging Galaxy NGC 3597 and its Population of Proto--Globular Clusters

We present wide field-of-view near-infrared imaging from the NTT and very deep optical imaging from the HST of the young merging galaxy NGC 3597. The morphology of the galaxy and the properties of the newly formed proto-globular clusters (PGCs) are examined. Our K band data reveals the presence of a second nucleus, which provides further evidence that NGC 3597 is the result of a recent merger. Combining new K band photometry with optical photometry, we are able for the first time to derive a unique age for the newly formed PGCs of a few Myrs. This is consistent with the galaxy starburst age of < 10 Myrs. From deep HST imaging, we are able to probe the luminosity function ~8 magnitudes fainter than normal, old globular clusters, and confirm that the PGCs have a power-law distribution with a slope of ~-2.Comment: 19 pages, Latex, 10 figures, 4 tables, accepted by MNRA

Evaluation of the soil moisture prediction accuracy of a space radar using simulation techniques

Image simulation techniques were employed to generate synthetic aperture radar images of a 17.7 km x 19.3 km test site located east of Lawrence, Kansas. The simulations were performed for a space SAR at an orbital altitude of 600 km, with the following sensor parameters: frequency = 4.75 GHz, polarization = HH, and angle of incidence range = 7 deg to 22 deg from nadir. Three sets of images were produced corresponding to three different spatial resolutions; 20 m x 20 m with 12 looks, 100 m x 100 m with 23 looks, and 1 km x 1 km with 1000 looks. Each set consisted of images for four different soil moisture distributions across the test site. Results indicate that, for the agricultural portion of the test site, the soil moisture in about 90% of the pixels can be predicted with an accuracy of = + or - 20% of field capacity. Among the three spatial resolutions, the 1 km x 1 km resolution gave the best results for most cases, however, for very dry soil conditions, the 100 m x 100 m resolution was slightly superior

Constraining dark energy fluctuations with supernova correlations

We investigate constraints on dark energy fluctuations using type Ia supernovae. If dark energy is not in the form of a cosmological constant, that is if the equation of state is not equal to -1, we expect not only temporal, but also spatial variations in the energy density. Such fluctuations would cause local variations in the universal expansion rate and directional dependences in the redshift-distance relation. We present a scheme for relating a power spectrum of dark energy fluctuations to an angular covariance function of standard candle magnitude fluctuations. The predictions for a phenomenological model of dark energy fluctuations are compared to observational data in the form of the measured angular covariance of Hubble diagram magnitude residuals for type Ia supernovae in the Union2 compilation. The observational result is consistent with zero dark energy fluctuations. However, due to the limitations in statistics, current data still allow for quite general dark energy fluctuations as long as they are in the linear regime.Comment: 18 pages, 6 figures, matches the published versio

Human central nervous system (CNS) ApoE isoforms are increased by age, differentially altered by amyloidosis, and relative amounts reversed in the CNS compared with plasma

The risk of Alzheimer's disease (AD) is highly dependent on apolipoprotein-E (apoE) genotype. The reasons for apoE isoform-selective risk are uncertain; however, both the amounts and structure of human apoE isoforms have been hypothesized to lead to amyloidosis increasing the risk for AD. To address the hypothesis that amounts of apoE isoforms are different in the human CNS, we developed a novel isoform-specific method to accurately quantify apoE isoforms in clinically relevant samples. The method utilizes an antibody-free enrichment step and isotope-labeled physiologically relevant lipoprotein particle standards produced by immortalized astrocytes. We applied this method to a cohort of well characterized clinical samples and observed the following findings. The apoE isoform amounts are not different in cerebrospinal fluid (CSF) from young normal controls, suggesting that the amount of apoE isoforms is not the reason for risk of amyloidosis prior to the onset of advanced age. We did, however, observe an age-related increase in both apoE isoforms. In contrast to normal aging, the presence of amyloid increased apoE3, whereas apoE4 was unchanged or decreased. Importantly, for heterozygotes, the apoE4/apoE3 isoform ratio was increased in the CNS, although the reverse was true in the periphery. Finally, CSF apoE levels, but not plasma apoE levels, correlated with CSF β-amyloid levels. Collectively, these findings support the hypothesis that CNS and peripheral apoE are separate pools and differentially regulated. Furthermore, these results suggest that apoE mechanisms for the risk of amyloidosis and AD are related to an interaction between apoE, aging, and the amount of amyloid burden

INCIDENCE OF HIGH GRADE QTCF PROLONGATION AND ITS MANAGEMENT AMONG PATIENTS UNDERGOING TREATMENT FOR DRUG RESISTANT TUBERCULOSIS (DR-TB): CASE SERIES.

Background: The World Health Organization (WHO) has approved the use of two new drugs, namely Bedaquiline (Bdq) and Delamanid (Dlm), for treatment of Drug Resistant Tuberculosis (DR-TB). One of the concerns raised with the use of these drugs was QT-interval prolongation. This condition could be serious and life threatening. Hence, knowing the magnitude and its management is very important. This case series identifies the incidence and discusses the management of clinically significant QT-interval prolongation amongst a cohort of patients who have been on these medicines. Materials and Methods: Patients with reports of high grade QT-Interval prolongation (i.e. Grade-3 and Grade-4) were identified from the cohort of 265 patients enrolled on bedaquiline and/delamanid and discussion is made on the pattern, severity and management of each cases identified. Results: Only 4 (1.5%) out of all 265 patients enrolled on Bedaquiline and/or Delamanid have developed high grade QT-Interval prolongation. And all are managed without permanent discontinuation of both drugs. Conclusion: The&nbsp;Incidence of&nbsp;clinically significant&nbsp;QTcF-interval prolongation among DR-TB&nbsp;patients&nbsp;taking bedaquiline and delamanid in Lesotho is low. And almost all cases can be managed with more frequent Electrocardiogram (ECG) monitoring and management of other possible causes of QT-interval prolongation without the need to stop one or both drugs permanentl

Time-resolved, multi-color photometry and spectroscopy of Virgo 4 (OU Vir): a high orbital inclination, short orbital period dwarf nova

We present multi-color photometry and time resolved spectroscopy of OU Vir. The analysis of the quiescent light curve shows that OU Vir is characterized by i) strong cycle-to-cycle brightness variations, and ii) hot spot modulated light curve with grazing eclipse of the impact region. Colors are derived both in- and out- of eclipse. The time-resolved spectroscopy allows us to produce the radial velocity curve from the H$\alpha$ accretion disk emission line which possibly reveals only weak evidence for hot spot line emission. The hot spot is believed to be a turbulent optically thick region, producing mostly continuum emission.Comment: 8 pages (including figures), 7 figures. To Be published in A&

PDS 144: the first confirmed Herbig Ae-Herbig Ae wide binary

PDS 144 is a pair of Herbig Ae stars that are separated by 5.'' 35 on the sky. It has previously been shown to have an A2Ve Herbig Ae star viewed at 83 degrees inclination as its northern member and an A5Ve Herbig Ae star as its southern member. Direct imagery revealed a disk occulting PDS 144 N-the first edge-on disk observed around a Herbig Ae star. The lack of an obvious disk in direct imagery suggested PDS 144 S might be viewed face-on or not physically associated with PDS 144 N. Multi-epoch Hubble Space Telescope imagery of PDS 144 with a 5 year baseline demonstrates PDS 144 N & S are comoving and have a common proper motion with TYC 6782-878-1. TYC 6782-878-1 has previously been identified as a member of Upper Sco sub-association A at d = 145 +/- 2 pc with an age of 5-10 Myr. Ground-based imagery reveals jets and a string of Herbig-Haro knots extending 13' (possibly further) which are aligned to within 7 degrees +/- 6 degrees on the sky. By combining proper motion data and the absence of a dark mid-plane with radial velocity data, we measure the inclination of PDS 144 S to be i = 73 degrees +/- 7 degrees. The radial velocity of the jets from PDS 144 N & S indicates they, and therefore their disks, are misaligned by 25 degrees +/- 9 degrees. This degree of misalignment is similar to that seen in T Tauri wide binaries.Peer reviewe