Serum cholesterol and variant in cholesterol-related gene CETP predict white matter microstructure

Several common genetic variants influence cholesterol levels, which play a key role in overall health. Myelin synthesis and maintenance are highly sensitive to cholesterol concentrations, and abnormal cholesterol levels increase the risk for various brain diseases, including Alzheimer's disease. We report significant associations between higher serum cholesterol (CHOL) and high-density lipoprotein levels and higher fractional anisotropy in 403 young adults (23.8 ± 2.4years) scanned with diffusion imaging and anatomic magnetic resonance imaging at 4Tesla. By fitting a multi-locus genetic model within white matter areas associated with CHOL, we found that a set of 18 cholesterol-related, single-nucleotide polymorphisms implicated in Alzheimer's disease risk predicted fractional anisotropy. We focused on the single-nucleotide polymorphism with the largest individual effects, CETP (rs5882), and found that increased G-allele dosage was associated with higher fractional anisotropy and lower radial and mean diffusivities in voxel-wise analyses of the whole brain. A follow-up analysis detected white matter associations with rs5882 in the opposite direction in 78 older individuals (74.3 ± 7.3years). Cholesterol levels may influence white matter integrity, and cholesterol-related genes may exert age-dependent effects on the brain

Diffusion MRI Indices and Their Relation to Cognitive Impairment in Brain Aging: The Updated Multi-protocol Approach in ADNI3

Brain imaging with diffusion-weighted MRI (dMRI) is sensitive to microstructural white matter (WM) changes associated with brain aging and neurodegeneration. In its third phase, the Alzheimer’s Disease Neuroimaging Initiative (ADNI3) is collecting data across multiple sites and scanners using different dMRI acquisition protocols, to better understand disease effects. It is vital to understand when data can be pooled across scanners, and how the choice of dMRI protocol affects the sensitivity of extracted measures to differences in clinical impairment. Here, we analyzed ADNI3 data from 317 participants (mean age: 75.4 ± 7.9 years; 143 men/174 women), who were each scanned at one of 47 sites with one of six dMRI protocols using scanners from three different manufacturers. We computed four standard diffusion tensor imaging (DTI) indices including fractional anisotropy (FADTI) and mean, radial, and axial diffusivity, and one FA index based on the tensor distribution function (FATDF), in 24 bilaterally averaged WM regions of interest. We found that protocol differences significantly affected dMRI indices, in particular FADTI. We ranked the diffusion indices for their strength of association with four clinical assessments. In addition to diagnosis, we evaluated cognitive impairment as indexed by three commonly used screening tools for detecting dementia and AD: the AD Assessment Scale (ADAS-cog), the Mini-Mental State Examination (MMSE), and the Clinical Dementia Rating scale sum-of-boxes (CDR-sob). Using a nested random-effects regression model to account for protocol and site, we found that across all dMRI indices and clinical measures, the hippocampal-cingulum and fornix (crus)/stria terminalis regions most consistently showed strong associations with clinical impairment. Overall, the greatest effect sizes were detected in the hippocampal-cingulum (CGH) and uncinate fasciculus (UNC) for associations between axial or mean diffusivity and CDR-sob. FATDF detected robust widespread associations with clinical measures, while FADTI was the weakest of the five indices for detecting associations. Ultimately, we were able to successfully pool dMRI data from multiple acquisition protocols from ADNI3 and detect consistent and robust associations with clinical impairment and age

Opera and Hypnosis: Victor Maurel’s Experiments with Verdi’s Otello

One day in his private home on the avenue Bugeaud, in Paris’s sixteenth arrondissement, the famous baritone Victor Maurel hosted a meeting which combined music with hypnotism of a young woman

Vocal Culture in the Age of Laryngoscopy

For several months beginning in 1884, readers of Life, Science, Health, the Atlantic Monthly and similar magazines would have encountered half-page advertisements for a newly patented medical device called the ‘ammoniaphone’ (Figure 2.1). Invented and promoted by a Scottish doctor named Carter Moffat and endorsed by the soprano Adelina Patti, British Prime Minister William Gladstone and the Princess of Wales, the ammoniaphone promised a miraculous transformation in the voices of its users. It was recommended for ‘vocalists, clergymen, public speakers, parliamentary men, readers, reciters, lecturers, leaders of psalmody, schoolmasters, amateurs, church choirs, barristers, and all persons who have to use their voices professionally, or who desire to greatly improve their speaking or singing tones’. Some estimates indicated that Moffat sold upwards of 30,000 units, yet the ammoniaphone was a flash in the pan as far as such things go, fading from public view after 1886

Unsound Seeds

With this image of a curtain hiding and at the same time heightening some terrible secret, Max Kalbeck began his review of the first Viennese performance of Richard Strauss’s Salome. Theodor W. Adorno picked up the image of the curtain in the context of Strauss’s fabled skill at composing non-musical events, when he identified the opening flourish of Strauss’s Salome as the swooshing sound of the rising curtain. If this is so, the succès de scandale of the opera was achieved, in more than one sense, as soon as the curtain rose at Dresden’s Semperoper on 10 December 1905. Critics of the premiere noted that the opera set ‘boundless wildness and degeneration to music’; it brought ‘high decadence’ onto the operatic stage; a ‘composition of hysteria’, reflecting the ‘disease of our time’, Salome is ‘hardly music any more’.The outrage did not end there

Science, Technology and Love in Late Eighteenth-Century Opera

It is a tale told by countless operas: young love, thwarted by an old man’s financially motivated marriage plans, triumphs in the end thanks to a deception that tricks the old man into blessing the young lovers’ union. Always a doddering fool, the old man is often also an enthusiast for knowledge. Such is the case, for instance, in Carlo Goldoni’s comic opera libretto Il mondo della luna (1750), in which Buonafede’s interest in the moon opens him to an elaborate hoax that has him believe he and his daughters have left Earth for the lunar world; and also in the Singspiel Die Luftbälle, oder der Liebhaber à la Montgolfier (1788), wherein the apothecary Wurm trades Sophie, the ward he intended to marry himself, for a technological innovation that will make him a pioneering aeronaut

Operatic Fantasies in Early Nineteenth-Century Psychiatry

In his celebrated essay on insanity in the Dictionnaire des sciences médicales (1816), French psychiatrist Étienne Esquirol marvelled at the earlier custom of allowing asylum inmates to attend theatrical productions at Charenton

Linda Ash, whose trailer was condemned because it lacked running water, spends t

Linda Ash, whose trailer was condemned because it lacked running water, spends time at Rockin\u27 Rickey\u27s Tavern in Portland, which feels like home and sleeps under a bridge. She says she had seven children by the age of 23 and toured under the stage name Linda Mae, singing country tunes. She hopes to find low-income housing by January

Thiol-disulfide organization in alliin lyase (alliinase) from garlic (Allium sativum)

Alliinase, an enzyme found in garlic, catalyzes the synthesis of the well-known chemically and therapeutically active compound allicin (diallyl thiosulfinate). The enzyme is a homodimeric glycoprotein that belongs to the fold-type I family of pyridoxal-5′-phosphate-dependent enzymes. There are 10 cysteine residues per alliinase monomer, eight of which form four disulfide bridges and two are free thiols. Cys368 and Cys376 form a S—S bridge located near the C-terminal and plays an important role in maintaining both the rigidity of the catalytic domain and the substrate-cofactor relative orientation. We demonstrated here that the chemical modification of allinase with the colored —SH reagent N-(4-dimethylamino-3,5-dinitrophenyl) maleimide yielded chromophore-bearing peptides and showed that the Cys220 and Cys350 thiol groups are accesible in solution. Moreover, electron paramagnetic resonance kinetic measurements using disulfide containing a stable nitroxyl biradical showed that the accessibilities of the two —SH groups in Cys220 and Cys350 differ. Neither enzyme activity nor protein structure (measured by circular dichroism) were affected by the chemical modification of the free thiols, indicating that alliinase activity does not require free —SH groups. This allowed the oriented conjugation of alliinase, via the —SH groups, with low- or high-molecular-weight molecules as we showed here. Modification of the alliinase thiols with biotin and their subsequent binding to immobilized streptavidin enabled the efficient enzymatic production of allicin