CSF T-Tau/Aβ42 Predicts White Matter Microstructure in Healthy Adults at Risk for Alzheimer’s Disease

Cerebrospinal fluid (CSF) biomarkers T-Tau and Aβ42 are linked with Alzheimer’s disease (AD), yet little is known about the relationship between CSF biomarkers and structural brain alteration in healthy adults. In this study we examined the extent to which AD biomarkers measured in CSF predict brain microstructure indexed by diffusion tensor imaging (DTI) and volume indexed by T1-weighted imaging. Forty-three middle-aged adults with parental family history of AD received baseline lumbar puncture and MRI approximately 3.5 years later. Voxel-wise image analysis methods were used to test whether baseline CSF Aβ42, total tau (T-Tau), phosphorylated tau (P-Tau) and neurofilament light protein predicted brain microstructure as indexed by DTI and gray matter volume indexed by T1-weighted imaging. T-Tau and T-Tau/Aβ42 were widely correlated with indices of brain microstructure (mean, axial, and radial diffusivity), notably in white matter regions adjacent to gray matter structures affected in the earliest stages of AD. None of the CSF biomarkers were related to gray matter volume. Elevated P-Tau and P-Tau/Aβ42 levels were associated with lower recognition performance on the Rey Auditory Verbal Learning Test. Overall, the results suggest that CSF biomarkers are related to brain microstructure in healthy adults with elevated risk of developing AD. Furthermore, the results clearly suggest that early pathological changes in AD can be detected with DTI and occur not only in cortex, but also in white matter

Synthesis, characterization and in vitro antitumor activities of binary and heterobimetallic complexes of oxovanadium(IV), manganese(II), iron(II,III), cobalt(II,III), nickel(II), copper(II) & zinc(II) with <i>p</i> -hydroxy dithiobenzoate

992-997A few complexes of the types M (p &ndash;Ohdtb)2 [M=Mn(II), Cu(II) or Zn(II)], M(p -OHdtb)3 [M=Fe(Ill) or co(III)], V(p-OHdtb)4 and Ni(p-OHdtbS) (p-OHdtb = p hydroxy dithiobenzoate] and heterobimetallic complexes M[Cd(p -OHdtb)4] [M=VO2+, Mn(II), Fe(II), Co(II), Ni(II) or Zn(II) have been prepared in water ethanol medium. The complexes have been characterized by elemental analyses, magnetic susceptibility measurements, and UV-VIS, IR, ESR and NMR (1H and !3C) spectral studies. In vitro results of the binary complexes on P-815 (murine mastocytoma) indicate that the complexes show significant inhibition on 3H-thymidine and 3H-uridine incorporation in tumor cells and thus inhibit DNA and RNA replications

Asp 187 and Phe 190 residues in lethal factor are required for the expression of anthrax lethal toxin activity

Anthrax toxin consists of three proteins, protective antigen, lethal factor, and edema factor. Protective antigen translocates lethal factor and edema factor to the cytosol of mammalian cells. The amino-termini of lethal factor and edema factor have several homologous stretches. These regions are presumably involved in binding to protective antigen. In the present study we have determined the role of one such homologous stretch in lethal factor. Residues 187AspLeuLeuPhe190 were replaced by alanine. Asp187Ala and Phe190Ala were found to be non-toxic in combination with protective antigen. Their protective antigen-binding ability was drastically reduced. We propose that Asp187 and Phe190 are crucial for the expression of anthrax lethal toxin activity

Awareness, knowledge, and risks of zoonotic diseases among livestock farmers in Punjab

Aim: The present study was conducted to assess the awareness, knowledge, and risks of zoonotic diseases among livestock farmers in Punjab. Materials and Methods: 250 livestock farmers were selected randomly and interviewed with a pretested questionnaire, which contained both open and close ended questions on different aspects of zoonotic diseases, i.e., awareness, knowledge, risks, etc. Knowledge scorecard was developed, and each correct answer was awarded one mark, and each incorrect answer was given zero mark. Respondents were categorized into low (mean − ½ standard deviation [SD]), moderate (mean ± ½ SD), and high knowledge (Mean + ½ SD) category based on the mean and SD. The information about independent variables viz., age, education, and herd size were collected with the help of structured schedule and scales. The data were analyzed by ANOVA, and results were prepared to assess awareness, knowledge, and risks of zoonotic diseases and its relation with independent variables. Results: Majority of the respondents had age up to 40 years (70%), had their qualification from primary to higher secondary level (77.6%), and had their herd size up to 10 animals (79.6%). About 51.2% and 54.0% respondents had the history of abortion and retained placenta, respectively, at their farms. The respondents not only disposed off the infected placenta (35.6%), aborted fetus (39.6%), or feces (56.4%) from a diarrheic animal but also gave intrauterine medication (23.2%) bare-handedly. About 3.6-69.6% respondents consumed uncooked or unpasteurized animal products. About 84.8%, 46.0%, 32.8%, 4.61%, and 92.4% of livestock farmers were aware of zoonotic nature of rabies, brucellosis, tuberculosis, anthrax, and bird flu, respectively. The 55.6%, 67.2%, 52.0%, 64.0%, and 51.2% respondents were aware of the transmission of zoonotic diseases to human being through contaminated milk, meat, air, feed, or through contact with infected animals, respectively. The transmission of rabies through dog bite (98.4%), need of post-exposure vaccination (96.8%), and annual vaccination of dogs (78%) were well-known facts but only 47.2% livestock owners were aware of the occurrence of abortion due to brucellosis and availability of prophylactic vaccine (67.6%) against it as a preventive measure. About 69.2% respondents belonged to low to medium knowledge level categories, whereas 30.8% respondents had high knowledge (p<0.05) regarding different aspects of zoonotic diseases. Age, education, and herd size had no significant effect on the knowledge level and awareness of farmers toward zoonotic diseases. Conclusion: Therefore, from the present study, it may be concluded that there is a need to create awareness and improve knowledge of livestock farmers toward zoonotic diseases for its effective containment in Punjab

T-Tau/Aβ42 Plotted against mean, radial, and axial diffusivity.

<p>Shown here are the results of the voxel-wise analysis, where regions with color overlay are those where higher T-Tau/Aβ42 was associated with higher diffusivity (mean, radial, and axial). In order to illustrate the relationship between T-Tau/Aβ42 and the diffusivity maps, we extracted diffusion values from representative regions of significant correlation in the voxel-wise analysis and plotted them against T-Tau/Aβ42. Shown on the top row are diffusion values extracted from the left temporal lobe (x = −42, y = −34, z = −16) plotted against T-Tau/Aβ42. In the middle row are diffusion values extracted from right posterior cingulum bundle (x = 8, y = −46, z = 16) plotted against T-Tau/Aβ42. In the bottom row are diffusion values extracted from left inferior frontal white matter (x = −22, y = 43, z = −12) plotted against T-Tau/Aβ42. Blue crosshairs overlaid on the brain sections indicate the location of the extracted values. Each point in the scatter represents diffusion values from one participant (n = 43). T-Tau/Aβ42 values were log-transformed and mean, radial, and axial diffusivity values were adjusted for age at time of scan, sex, and treatment (CSF data were collected at baseline in a Simvastatin treatment trial, data from the prevention trial are not shown here).</p

Linear correlation among CSF biomarkers and age.

<p>Significant correlation at P<.05 *.</p><p>Significant at p<.001 Ŧ.</p

Percent of regional overlap between statistical parametric mapping result maps.

<p>All results maps were the product of a linear correlation analysis, where the CSF measures (T-Tau and T-Tau/Aβ42) were used to predict the diffusion measures (MD, axial and radial diffusivity). T-Tau: Total Tau; MD: Mean Diffusivity; Rad: Radial; Ax: Axial; Diff: Diffusivity.</p>*<p>Result map shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0037720#pone-0037720-g001" target="_blank">Figure 1</a>.</p