Tau filaments are tethered within brain extracellular vesicles in Alzheimer’s disease

The abnormal assembly of tau protein in neurons is the pathological hallmark of multiple neurodegenerative diseases, including Alzheimer’s disease (AD). In addition, assembled tau associates with extracellular vesicles (EVs) in the central nervous system of patients with AD, which is linked to its clearance and prion-like propagation between neurons. However, the identities of the assembled tau species and the EVs, as well as how they associate, are not known. Here, we combined quantitative mass spectrometry, cryo-electron tomography and single-particle cryo-electron microscopy to study brain EVs from AD patients. We found filaments of truncated tau enclosed within EVs enriched in endo-lysosomal proteins. We observed multiple filament interactions, including with molecules that tethered filaments to the EV limiting membrane, suggesting selective packaging. Our findings will guide studies into the molecular mechanisms of EV-mediated secretion of assembled tau and inform the targeting of EV-associated tau as potential therapeutic and biomarker strategies for AD

Seasonal time-series modeling and forecasting of monthly mean temperature for decision making in the Kurdistan Region of Iraq

A generalized structural time-series modeling framework was used to analyze the monthly records of mean temperature, one of the most important environmental parameters, using classical stochastic processes. In this article we are using the SARIMA Box–Jenkins model and obtain a medium-term (10 years) forecast of the mean temperature in Erbil. A prediction of the monthly mean temperature during the past 287 months ((Formula presented.)24 years) using the SARIMA(0,1,2)(0,1,1)12 model predicts that the average temperature in the governorate of Erbil, Iraq, will be stable for the next 10 years. The evaluation of prediction accuracy shows that our model performs equally well when applying it to different periods of time for which data is available. The method used here could easily be applied by the decision makers responsible for providing water and electricity in the Kurdistan Region

Spatially resolved transcriptomics reveals genes associated with the vulnerability of middle temporal gyrus in Alzheimer’s disease

Human middle temporal gyrus (MTG) is a vulnerable brain region in early Alzheimer’s disease (AD), but little is known about the molecular mechanisms underlying this regional vulnerability. Here we utilize the 10 × Visium platform to define the spatial transcriptomic profile in both AD and control (CT) MTG. We identify unique marker genes for cortical layers and the white matter, and layer-specific differentially expressed genes (DEGs) in human AD compared to CT. Deconvolution of the Visium spots showcases the significant difference in particular cell types among cortical layers and the white matter. Gene co-expression analyses reveal eight gene modules, four of which have significantly altered co-expression patterns in the presence of AD pathology. The co-expression patterns of hub genes and enriched pathways in the presence of AD pathology indicate an important role of cell–cell-communications among microglia, oligodendrocytes, astrocytes, and neurons, which may contribute to the cellular and regional vulnerability in early AD. Using single-molecule fluorescent in situ hybridization, we validated the cell-type-specific expression of three novel DEGs (e.g., KIF5A, PAQR6, and SLC1A3) and eleven previously reported DEGs associated with AD pathology (i.e., amyloid beta plaques and intraneuronal neurofibrillary tangles or neuropil threads) at the single cell level. Our results may contribute to the understanding of the complex architecture and neuronal and glial response to AD pathology of this vulnerable brain region

Influences of the North Atlantic oscillation on precipitation variability and changes in Turkey

Workshop on Historical Reconstruction of Climate Variability and Change in Mediterranean Regions -- OCT 05-06, 2004 -- Bologna, ITALYWOS: 000237375500015The anomalous circulations at 500-hPa geopotential level during the extreme North Atlantic Oscillation Index (NAOI) phases were investigated in order to explain atmospheric causes of the changes in precipitation of the 78 stations of Turkey during the extreme NAOI phases. We arranged and analysed the 500-hPa height data of the 231 grid points for a large region delimited by the 40 degrees W and 60 degrees E longitudes and by the 20 degrees N and 70 degrees N latitudes. The main conclusions of the study are as follows: 1) Annual, winter, spring, autumn and partly summer composite precipitation means are mostly characterised by wetter than long-term average conditions during the negative NAOI phase, whereas the positive NAOI responses mostly exhibit drier than long-term average conditions annually and in all seasons except summer. 2) Spatially coherent and statistically significant changes in the precipitation amounts during the extreme NAOI phases, are more apparent in the west and mid Turkey. 3) The 500-hPa circulation corresponding to the negative NAOI phase brings above long-term average precipitation to Turkey in winter; spring and autumn and annually, associated with the NAO pattern in which the 500-hPa geopotential level is anomalously high in the area of the Icelandic Low and anomalously low across the regions of the Azores High and the Europe in general. 4) Contrary, the NAO pattern over the North Atlantic and the Europe is responsible for the drier than long-term average precipitation conditions in Turkey during the positive NAOI phase, when the 500-hPa geopotential level is anomalously low over the area of the Icelandic Low and the anomalously high across the subtropical and mid-latitude north-east Atlantic and the Europe regions

Tumor markers. Consensus Conference on Diagnosis and Prognostic Parameters in Localized Prostate Cancer. Stockholm, Sweden, May 12-13, 1993

This chapter mainly deals with biochemical aspects on prostate specific antigen (PSA) and its clinical value. To a limited extent, also other tumor markers, which might be of importance in the evaluation of patients with prostate cancer are discussed. In serum, PSA exists in a free form or bound to antichymotrypsin. Interestingly, only 10% of PSA secreted from cancer cells seems to exist in a free form, as compared to 30% of PSA secreted from cells in benign prostatic hyperplasia (BPH). PSA seems to be closely, but not absolutely, related to tumor grade and stage. The mean value of PSA in patients with tumors dominated by Gleason grades 3 or below, was 10 ng/ml, compared to 29 ng/ml in those with higher grades. Patients with PSA values of 50 ng/ml or above almost exclusively had tumor of Gleason grades 4 or 5, and this limit usually reflected a generalized disease. Patients with PSA-values below 10 ng/ml almost exclusively had tumors confined to the prostate gland. In countries where screening for prostate cancer is believed in, it is important to understand that normal cut-off values are related to patient's age. The upper normal limit of males below 50 years of age should be set at 2.5 ng/ml, as compared to 6.5 ng/ml for men over 70 years of age. To improve the value of PSA determination and for scientific purposes, the standardization of the assay is urgently needed and under way. Prostate acid phosphatase (PAP) has in most centres been replaced by PSA. An elevated PAP value, as measured by the enzymatic method, invariably indicates a generalized disease and could thus be used as a complementary informative assay to PSA. Other markers have been used mainly to achieve additional prognostic information. In a multivariate analysis, the non-specific tumor marker neopterin, which reflects the host response to tumor antigens, was closely related to short-term prognosis. Neopterin was followed by thymidine kinase, a protein reflecting the cell turn-over and tumor grade. Also PSA at diagnosis seemed to add some prognostic information, whereas other markers did not