Clinical and Biomarker Changes in Dominantly Inherited Alzheimer's Disease

BACKGROUND: The order and magnitude of pathologic processes in Alzheimer's disease are not well understood, partly because the disease develops over many years. Autosomal dominant Alzheimer's disease has a predictable age at onset and provides an opportunity to determine the sequence and magnitude of pathologic changes that culminate in symptomatic disease. METHODS: In this prospective, longitudinal study, we analyzed data from 128 participants who underwent baseline clinical and cognitive assessments, brain imaging, and cerebrospinal fluid (CSF) and blood tests. We used the participant's age at baseline assessment and the parent's age at the onset of symptoms of Alzheimer's disease to calculate the estimated years from expected symptom onset (age of the participant minus parent's age at symptom onset). We conducted cross-sectional analyses of baseline data in relation to estimated years from expected symptom onset in order to determine the relative order and magnitude of pathophysiological changes. RESULTS: Concentrations of amyloid-beta (Aβ)(42) in the CSF appeared to decline 25 years before expected symptom onset. Aβ deposition, as measured by positron-emission tomography with the use of Pittsburgh compound B, was detected 15 years before expected symptom onset. Increased concentrations of tau protein in the CSF and an increase in brain atrophy were detected 15 years before expected symptom onset. Cerebral hypometabolism and impaired episodic memory were observed 10 years before expected symptom onset. Global cognitive impairment, as measured by the Mini-Mental State Examination and the Clinical Dementia Rating scale, was detected 5 years before expected symptom onset, and patients met diagnostic criteria for dementia at an average of 3 years after expected symptom onset. CONCLUSIONS: We found that autosomal dominant Alzheimer's disease was associated with a series of pathophysiological changes over decades in CSF biochemical markers of Alzheimer's disease, brain amyloid deposition, and brain metabolism as well as progressive cognitive impairment. Our results require confirmation with the use of longitudinal data and may not apply to patients with sporadic Alzheimer's disease. (Funded by the National Institute on Aging and others; DIAN ClinicalTrials.gov number, NCT00869817.)

A Vehicle Trajectory Privacy Preservation Method Based on Caching and Dummy Locations in the Internet of Vehicles

In the internet of vehicles (IoVs), vehicle users should provide location information continuously when they want to acquire continuous location-based services (LBS), which may disclose the vehicle trajectory privacy. To solve the vehicle trajectory privacy leakage problem in the continuous LBS, we propose a vehicle trajectory privacy preservation method based on caching and dummy locations, abbreviated as TPPCD, in IoVs. In the proposed method, when a vehicle user wants to acquire a continuous LBS, the dummy locations-based location privacy preservation method under road constraint is used. Moreover, the cache is deployed at the roadside unit (RSU) to reduce the information interaction between vehicle users covered by the RSU and the LBS server. Two cache update mechanisms, the active cache update mechanism based on data popularity and the passive cache update mechanism based on dummy locations, are designed to protect location privacy and improve the cache hit rate. The performance analysis and simulation results show that the proposed vehicle trajectory privacy preservation method can resist the long-term statistical attack (LSA) and location correlation attack (LCA) from inferring the vehicle trajectory at the LBS server and protect vehicle trajectory privacy effectively. In addition, the proposed cache update mechanisms achieve a high cache hit rate

Composition and expression of genes encoding carbohydrate-active enzymes in the straw-degrading mushroom Volvariella volvacea.

Volvariella volvacea is one of a few commercial cultivated mushrooms mainly using straw as carbon source. In this study, the genome of V. volcacea was sequenced and assembled. A total of 285 genes encoding carbohydrate-active enzymes (CAZymes) in V. volvacea were identified and annotated. Among 15 fungi with sequenced genomes, V. volvacea ranks seventh in the number of genes encoding CAZymes. In addition, the composition of glycoside hydrolases in V. volcacea is dramatically different from other basidiomycetes: it is particularly rich in members of the glycoside hydrolase families GH10 (hemicellulose degradation) and GH43 (hemicellulose and pectin degradation), and the lyase families PL1, PL3 and PL4 (pectin degradation) but lacks families GH5b, GH11, GH26, GH62, GH93, GH115, GH105, GH9, GH53, GH32, GH74 and CE12. Analysis of genome-wide gene expression profiles of 3 strains using 3'-tag digital gene expression (DGE) reveals that 239 CAZyme genes were expressed even in potato destrose broth medium. Our data also showed that the formation of a heterokaryotic strain could dramatically increase the expression of a number of genes which were poorly expressed in its parental homokaryotic strains

Ground Radioactivity Distribution Reconstruction and Dose Rate Estimation Based on Spectrum Deconvolution

Estimating the gamma dose rate at one meter above ground level and determining the distribution of radioactive pollution from aerial radiation monitoring data are the core technical issues of unmanned aerial vehicle nuclear radiation monitoring. In this paper, a reconstruction algorithm of the ground radioactivity distribution based on spectral deconvolution was proposed for the problem of regional surface source radioactivity distribution reconstruction and dose rate estimation. The algorithm estimates unknown radioactive nuclide types and their distributions using spectrum deconvolution and introduces energy windows to improve the accuracy of the deconvolution results, achieving accurate reconstruction of multiple continuous distribution radioactive nuclides and their distributions, as well as dose rate estimation of one meter above ground level. The feasibility and effectiveness of the method were verified through cases of single-nuclide (137Cs) and multi-nuclide (137Cs and 60Co) surface sources by modeling and solving them. The results showed that the cosine similarities between the estimated ground radioactivity distribution and dose rate distribution with the true value were 0.9950 and 0.9965, respectively, which could prove that the proposed reconstruction algorithm would effectively distinguish multiple radioactive nuclides and accurately restore their radioactivity distribution. Finally, the influences of statistical fluctuation levels and the number of energy windows on the deconvolution results were analyzed, showing that the lower the statistical fluctuation level and the more energy window divisions, the better the deconvolution results

Major characteristics of DGE libraries.

<p>Major characteristics of DGE libraries.</p

Double clustering of the carbohydrate-cleaving families of 8 basidiomycete genomes.

<p><b>Top tree:</b> S. com. for <i>Schizophyllum commune</i>; V. vol. for <i>Volvariella volvacea</i>; P. chr. for <i>Phanerochaete chrysosporium</i>; C. cin. for <i>Coprinopsis cinerea</i>; P. pla. for <i>Postia placenta</i>; L. bio. for <i>Laccaria bicolor</i>; C. neo. for <i>Cryptococcus neoformans</i>; U. may. for <i>Ustilago maydis</i>. <b>Left tree:</b> the enzyme families are represented by their class (GH for glycoside hydrolase; PL for polysaccharide lyase; CE for carbohydrate esterase) and family number according to the carbohydrate-active enzyme database <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058780#pone.0058780-Cantarel1" target="_blank">[23]</a>. <b>Right side:</b> known substrate of CAZy families. Abundance of the different enzymes within a family is represented by a colour scale from 0 (black) to >20 (red) occurrences per species.</p

Gene expression in three strains of <i>V. volvacea</i>.

<p>(<b>a</b>) Venn diagrams showing genes expressed in the three strains. (<b>b</b>) The histogram shows the percentage of genes that are differentially expressed in the three strains of <i>V. volvacea</i>.</p

Effects of the formation of heterokaryon on gene expression.

a<p>TMP: Tags per million.</p

The colonial characteristics of <i>V. volvacea</i> stains PYd15(a, b), H1521(c, d) and PYd21(e, f).

<p>(a,c,e). strains were growth on PDA plates and images were captured after 4 d of growth. (b,d,f). strains were growth on a straw-based medium and images were captured after 15 d of cultivation.</p