Distribution patterns of tau pathology in progressive supranuclear palsy

Progressive supranuclear palsy (PSP) is a 4R-tauopathy predominated by subcortical pathology in neurons, astrocytes, and oligodendroglia associated with various clinical phenotypes. In the present international study, we addressed the question of whether or not sequential distribution patterns can be recognized for PSP pathology. We evaluated heat maps and distribution patterns of neuronal, astroglial, and oligodendroglial tau pathologies and their combinations in different clinical subtypes of PSP in postmortem brains. W

Serum magnesium and calcium levels in relation to ischemic stroke : Mendelian randomization study

ObjectiveTo determine whether serum magnesium and calcium concentrations are causally associated with ischemic stroke or any of its subtypes using the mendelian randomization approach.MethodsAnalyses were conducted using summary statistics data for 13 single-nucleotide polymorphisms robustly associated with serum magnesium (n = 6) or serum calcium (n = 7) concentrations. The corresponding data for ischemic stroke were obtained from the MEGASTROKE consortium (34,217 cases and 404,630 noncases).ResultsIn standard mendelian randomization analysis, the odds ratios for each 0.1 mmol/L (about 1 SD) increase in genetically predicted serum magnesium concentrations were 0.78 (95% confidence interval [CI] 0.69-0.89; p = 1.3 7 10-4) for all ischemic stroke, 0.63 (95% CI 0.50-0.80; p = 1.6 7 10-4) for cardioembolic stroke, and 0.60 (95% CI 0.44-0.82; p = 0.001) for large artery stroke; there was no association with small vessel stroke (odds ratio 0.90, 95% CI 0.67-1.20; p = 0.46). Only the association with cardioembolic stroke was robust in sensitivity analyses. There was no association of genetically predicted serum calcium concentrations with all ischemic stroke (per 0.5 mg/dL [about 1 SD] increase in serum calcium: odds ratio 1.03, 95% CI 0.88-1.21) or with any subtype.ConclusionsThis study found that genetically higher serum magnesium concentrations are associated with a reduced risk of cardioembolic stroke but found no significant association of genetically higher serum calcium concentrations with any ischemic stroke subtype

FUT2 Variants Confer Susceptibility to Familial Otitis Media

Non-secretor status due to homozygosity for the common FUT2 variant c.461G>A (p.Trp154∗) is associated with either risk for autoimmune diseases or protection against viral diarrhea and HIV. We determined the role of FUT2 in otitis media susceptibility by obtaining DNA samples from 609 multi-ethnic families and simplex case subjects with otitis media. Exome and Sanger sequencing, linkage analysis, and Fisher exact and transmission disequilibrium tests (TDT) were performed. The common FUT2 c.604C>T (p.Arg202∗) variant co-segregates with otitis media in a Filipino pedigree (LOD = 4.0). Additionally, a rare variant, c.412C>T (p.Arg138Cys), is associated with recurrent/chronic otitis media in European-American children (p = 1.2 × 10−5) and US trios (TDT p = 0.01). The c.461G>A (p.Trp154∗) variant was also over-transmitted in US trios (TDT p = 0.01) and was associated with shifts in middle ear microbiota composition (PERMANOVA p 20 were combined, FUT2 variants were over-transmitted in trios (TDT p = 0.001). Fut2 is transiently upregulated in mouse middle ear after inoculation with non-typeable Haemophilus influenzae. Four FUT2 variants—namely p.Ala104Val, p.Arg138Cys, p.Trp154∗, and p.Arg202∗—reduced A antigen in mutant-transfected COS-7 cells, while the nonsense variants also reduced FUT2 protein levels. Common and rare FUT2 variants confer susceptibility to otitis media, likely by modifying the middle ear microbiome through regulation of A antigen levels in epithelial cells. Our families demonstrate marked intra-familial genetic heterogeneity, suggesting that multiple combinations of common and rare variants plus environmental factors influence the individual otitis media phenotype as a complex trait

Association of common genetic variants with brain microbleeds

OBJECTIVE: To identify common genetic variants associated with the presence of brain microbleeds (BMBs). METHODS: We performed geno

Hantaviral mechanisms driving HLA class I antigen presentation require both RIG-I and TRIF

Stemcel biology/Regenerative medicine (incl. bloodtransfusion

Robust unidirectional OFDM-communication system: Integration in a drill string and measurements of the autarctic system

Deep drilling technologies use MWD (Measuring While Drilling) and LWD (Logging While Drilling) systems near the drill bit in order to gather large amounts of directional and geological information. The data are mostly processed downhole. To transmit the main results to the surface in nearly real time a high speed data communication system with more than 100 bit/s is highly advantageous. The most commonly usedprocessfor data transmission in boreholes is the so called mud pulse telemetry. However, mud pulse telemetry systems cannot transmit such high data rates. A significant improvement is expected through the use of acoustic waves along the drill string for data transmission. In the 1980s and 1990s there were some attempts to transmit the downhole data by means of acoustic signals along the metallic drill string to the surface. However, these trials were not much of a success, because the acoustic transmission channel of a real drill string was too complex for the applied modulation schemes. In details, a drill string channel configuration consisting of a large number of drill pipes and tooljoints with different diameters causes multiple signal reflections and depending on the superimposing of all reflections with the original signal, pass- and stop bands will be created. This limits the achievable data rate, because only thepassbands are suitable for use by data transmission. Moreover, the characteristics of the pass- and stop bands vary with each change in the drill string configuration. Because of such challenging issues, the acoustic transmission process is significantly complex. However, the deployment of new actuators in combination with latest state of the art techniques from mobile communications can overcome the mentioned difficulties. Such techniques enable for instance an adaptive bi-directional communication to be applied, whereby the data transmission can continuously be adapted to the changing channel characteristics. As a first step for the application of the acoustic communication system on a real drill string a prototype systemfor unidirectional communication (uplink transmission) was developed and built up. Due to their relatively large sizes (outer diameter: 11 1/4"), the current prototype components cannot be used in standard deep bottom hole assemblies. However, suitable drill strings for such prototype sizes are found in mining drilling operations, for example with raise bore drilling. Thus, the initial prototype components were designed to be integrated into a raise bore drill string. The highly robust communication concept was developed to allow initial data rates of up to 30 bit/s. The prototype transmitting system consists of two units. The first one is located downhole. It includes a generator, a battery and a transmitter-sub. Furthermore there is the surface unit, which includes a receiver module, a WLAN access point and a terminal computer. The downhole batteiy can be recharged by a downhole alternator, which is driven by the drilling mud. The receiver module is attached to the uppermost drill string element and connected via a WiFi module to the terminal computer. At the surface unit the received data will be decoded and evaluated. The communication system is ready to be tested on a real well to transmit different types of data to the surface and to decode them there. The data to be transmitted during the initial field test will include information about the battery status, the temperature of the downhole unit in addition to dynamic and directional drilling data. In order to test the application limits as well as the robustness of the novel acoustic data transmission system, the influence of different interferences and noise sources on the data transmission quality were to he investigated. Unfortunately, the field trial was delaved several times and in the end cancelled in the scope of this project. But results from laboratory tests are available. During these investigations with the new acoustic communication telemetry system several interfering signals were generated to simulate real operation. Water waspumped through the system and the mechanical interaction between the drill string and the borehole wall was reproduced by rubbing on the drill string with sandpaper and applying hammer scales as well as combinations thereof Although the induced interferences reduced the quality of the data stream, the data transmission along the drill string was still possible in the presence of any kind of interference. The next development step would be the implementation of an adaptive, bi-directional communication system. This already has been built up and tested in the laboratory setup. The bi-directional communication system will significantly increase the transmission rate