Neuroinflammation and Neuronal Loss Precede Aβ Plaque Deposition in the hAPP-J20 Mouse Model of Alzheimer’s Disease

Recent human trials of treatments for Alzheimer's disease (AD) have been largely unsuccessful, raising the idea that treatment may need to be started earlier in the disease, well before cognitive symptoms appear. An early marker of AD pathology is therefore needed and it is debated as to whether amyloid-βAβ? plaque load may serve this purpose. We investigated this in the hAPP-J20 AD mouse model by studying disease pathology at 6, 12, 24 and 36 weeks. Using robust stereological methods, we found there is no neuron loss in the hippocampal CA3 region at any age. However loss of neurons from the hippocampal CA1 region begins as early as 12 weeks of age. The extent of neuron loss increases with age, correlating with the number of activated microglia. Gliosis was also present, but plateaued during aging. Increased hyperactivity and spatial memory deficits occurred at 16 and 24 weeks. Meanwhile, the appearance of plaques and oligomeric Aβ were essentially the last pathological changes, with significant changes only observed at 36 weeks of age. This is surprising given that the hAPP-J20 AD mouse model is engineered to over-expresses Aβ. Our data raises the possibility that plaque load may not be the best marker for early AD and suggests that activated microglia could be a valuable marker to track disease progression.Funding provided by Iain S. Gray Foundation, Stanley and John Roth, Patricia A. Quick foundation, David King, Doug Battersby, Tony and Vivian Howland-Rose, Walter and Edith Sheldon, Gleneagle Securities, Bill Gruy, Geoffrey Towner, Amadeus Energy Ltd., Nick and Melanie Kell, J. O. and J. R. Wicking Trust and the Mason Foundation, the New South Wales Government, through their office for Science and Medical Research, and SpinalCure Australia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Hydrology and Earth System Sciences The International Soil Moisture Network: a data hosting facility for global in situ soil moisture measurements

Abstract. In situ measurements of soil moisture are invaluable for calibrating and validating land surface models and satellite-based soil moisture retrievals. In addition, longterm time series of in situ soil moisture measurements themselves can reveal trends in the water cycle related to climate or land cover change. Nevertheless, on a worldwide basis the number of meteorological networks and stations measuring soil moisture, in particular on a continuous basis, is still limited and the data they provide lack standardization of technique and protocol

Nitrate-responsive oral microbiome modulates nitric oxide homeostasis and blood pressure in humans

© 2018 The Author(s) Imbalances in the oral microbial community have been associated with reduced cardiovascular and metabolic health. A possible mechanism linking the oral microbiota to health is the nitrate (NO3-)-nitrite (NO2-)-nitric oxide (NO) pathway, which relies on oral bacteria to reduce NO3- to NO2-. NO (generated from both NO2- and L-arginine) regulates vascular endothelial function and therefore blood pressure (BP). By sequencing bacterial 16S rRNA genes we examined the relationships between the oral microbiome and physiological indices of NO bioavailability and possible changes in these variables following 10 days of NO3- (12 mmol/d) and placebo supplementation in young (18–22 yrs) and old (70–79 yrs) normotensive humans (n = 18). NO3- supplementation altered the salivary microbiome compared to placebo by increasing the relative abundance of Proteobacteria (+225%) and decreasing the relative abundance of Bacteroidetes (−46%; P < 0.05). After NO3-supplementation the relative abundances of Rothia (+127%) and Neisseria (+351%) were greater, and Prevotella (−60%) and Veillonella (−65%) were lower than in the placebo condition (all P < 0.05). NO3- supplementation increased plasma concentration of NO2- and reduced systemic blood pressure in old (70–79 yrs), but not young (18–22 yrs), participants. High abundances of Rothia and Neisseria and low abundances of Prevotella and Veillonella were correlated with greater increases in plasma [NO2-] in response to NO3- supplementation. The current findings indicate that the oral microbiome is malleable to change with increased dietary intake of inorganic NO3-, and that diet-induced changes in the oral microbial community are related to indices of NO homeostasis and vascular health in vivo

Using body mass index ignores the intensive training of elite special force personnel

Body mass index is a common and well-known measure in daily life. A body mass index higher than 25 is assumed to be an indicator for overweight and obesity and a high amount of total body fat. But body mass index overestimates body fat in subjects with high muscle mass and underestimates it in persons with a low lean body mass, especially in elderly and diseased persons. In the present study, we investigate the performance of the body mass index as a measure of body fatness and its ability to distinguish between well-trained and untrained subjects. Twenty-one well-trained male members of a police task force named “Cobra” and 38 non-active controls, matched by age, weight and height were participants of the study. The age range of these subjects was between 30 and 45 years. Subcutaneous adipose tissue thicknesses and body fat distributions were measured non-invasively by an optical device named the “Lipometer.” Statistics were performed with SPSS. We found that the body mass index did not show a difference between the two groups, whereas all Lipometer results were able to discriminate significantly between the trained and untrained subjects. Furthermore, the receiver operating characteristic curve analysis was calculated and all Lipometer measurements provided significant results up to a correct classification of all subjects of 86.4%, which was for the lateral thigh body site. In conclusion, the body mass index was not able to recognize the difference between trained and untrained participants, while body fat distribution measured with the Lipometer was able to distinguish more clearly the large body fat differences between these two groups

Estimation of tropospheric parameters with GNSS smartphones in a differential approach

With the introduction of the operating system Android 7 Nougat in the year 2016, it became possible to access Global Navigation Satellite System (GNSS) code and carrier phase observations. These observations can be processed with the state-of-the-art GNSS processing software packages, which allows an in-depth evaluation of the smartphone's GNSS performance. The availability of carrier phase observations enables sub-decimeter-level positioning. A few years ago, smartphones wearing dual-frequency GNSS chipsets hit the mass market. In this study, we investigate the capability of such a device for the estimation of tropospheric delays. Static measurements carried out over the period of two weeks are performed using a Google Pixel 4 XL smartphone. The measurements are processed using relative positioning methods with a baseline length of about 33 kilometers, where a continuously operating reference station (CORS) acts as a base. The estimated differential zenith tropospheric wet delay (dZWD), obtained for the smartphone are then combined with absolute values computed at the reference station, in order to obtain time series of Zenith Total Delay (ZTD). Using this method, we demonstrate that high-precision ZTDs can be successfully determined from smartphone GNSS observations. When comparing the estimated tropospheric delays with those determined at a nearby geodetic receiver to assess the accuracy of the acquired time series of ZTD, differences in the range of few millimeters to a centimeter are visible. We examine the impact of various error sources, such as antenna phase center variations and residual effects of the ionosphere. Given that the obtained accuracies are at the level of a centimeter and below, the suggested method shows the potential to resolve small-scale tropospheric structures in near real-time, and thus, could be an interesting data source for numerical weather prediction models or related GNSS crowdsourcing projects.ISSN:0957-0233ISSN:1361-650

Time course of disease progression, as a percentage of hAPP-J20 6-week-old mice.

<p>Mice exhibit 32% loss of neurons in the CA1 region of the hippocampus between 6 weeks and 36 weeks of age. In addition, a 163% increase in the number of CD68-positive microglia and a 62% increase in the number of CA1 GFAP-positive astrocytes occurred between 6 weeks and 36 weeks of age. Total Aβ expression increases by 242% between the ages of 6 weeks and 36 weeks of age. Small arrow represents plaque load in some mice, while larger arrow represents plaque load in all mice.</p