There are a number of ways in which a clinical diagnosis of dementia of the Alzheimer type can be made – the application of clinical criteria is the commonest but ancillary techniques such as neuroima

Clinical Diagnosis of Alzheimer's Disease

Heterochromatin has been defined as deeply staining chromosomal material that remains condensed in interphase, whereas euchromatin undergoes de-condensation. Heterochromatin is found near centromeres and telomeres, but interstitial sites of heterochromatin (knobs) are common in plant genomes and were first described in maize. These regions are repetitive and late-replicating. In Drosophila, heterochromatin influences gene expression, a heterochromatin phenomenon called position effect variegation. Similarities between position effect variegation in Drosophila and gene silencing in maize mediated by "controlling elements" (that is, transposable elements) led in part to the proposal that heterochromatin is composed of transposable elements, and that such elements scattered throughout the genome might regulate development. Using microarray analysis, we show that heterochromatin in Arabidopsis is determined by transposable elements and related tandem repeats, under the control of the chromatin remodelling ATPase DDM1 (Decrease in DNA Methylation 1). Small interfering RNAs (siRNAs) correspond to these sequences, suggesting a role in guiding DDM1. We also show that transposable elements can regulate genes epigenetically, but only when inserted within or very close to them. This probably accounts for the regulation by DDM1 and the DNA methyltransferase MET1 of the euchromatic, imprinted gene FWA, as its promoter is provided by transposable-element-derived tandem repeats that are associated with siRNAs.

Role of transposable elements in heterochromatin and epigenetic control

Cyclic nucleotide-gated (CNG) channels are nonselective cation channels first identified in retinal photoreceptors and olfactory sensory neurons (OSNs). They are opened by the direct binding of cyclic nucleotides, cAMP and cGMP. Although their activity shows very little voltage dependence, CNG channels belong to the superfamily of voltage-gated ion channels. Like their cousins the voltage-gated K+ channels, CNG channels form heterotetrameric complexes consisting of two or three different types of subunits. Six different genes encoding CNG channels, four A subunits (A1 to A4) and two B subunits (B1 and B3), give rise to three different channels in rod and cone photoreceptors and in OSNs. Important functional features of these channels, i.e., ligand sensitivity and selectivity, ion permeation, and gating, are determined by the subunit composition of the respective channel complex. The function of CNG channels has been firmly established in retinal photoreceptors and in OSNs. Studies on their presence in other sensory and nonsensory cells have produced mixed results, and their purported roles in neuronal pathfinding or synaptic plasticity are not as well understood as their role in sensory neurons. Similarly, the function of invertebrate homologs found in Caenorhabditis elegans, Drosophila, and Limulus is largely unknown, except for two subunits of C. elegans that play a role in chemosensation. CNG channels are nonselective cation channels that do not discriminate well between alkali ions and even pass divalent cations, in particular Ca2+. Ca2+ entry through CNG channels is important for both excitation and adaptation of sensory cells. CNG channel activity is modulated by Ca2+/calmodulin and by phosphorylation. Other factors may also be involved in channel regulation. Mutations in CNG channel genes give rise to retinal degeneration and color blindness. In particular, mutations in the A and B subunits of the CNG channel expressed in human cones cause various forms of complete and incomplete achromatopsia.

Cyclic Nucleotide-Gated Ion Channels

https://repositorio.uca.edu.ar/bitstream/123456789/1653/1/melatonin-pleiotropic-orchestrating-regulator-molecule.pdf

Melatonin—A pleiotropic, orchestrating regulator molecule

Human pineal physiology and functional significance of melatonin

Daily rhythm of serum melatonin in patients with dementia of the degenerate type

Mikroelektrodenableitung vom freigelegten Pinealorgan der Regenbogenforelle (Ableitung von einzelnen Ganglienzellen der Epiphysis cerebri bzw. Massenentladung von Nervenfasern des Tr. pinealis) zeigt eine spontane Impulsaktivitat, die durch Belichtung gehemmt wird und auch nach Entfernung der Lateralaugen bestehen bleibt. In der Regel ist die Antwort unabhangig von der Wellenlange des Reizlichts (achromatische Antwort), doch wurden in einigen Versuchen auch chromatische Antworten beobachtet. Die fur eine Reihe von Pinealorganen bei Salmo irideus bestimmte absolute (Hemmungs-)Schwelle liegt bei 3 · 10−5 lm/m2 (Massenentladung) und bei 7 · 10−5 lm/m2 (Einzelneurone) gegenuber Lichtreizen von 1 sec Dauer, und bei 2,5 · 10−6 lm/m2 gegenuber Dauerlicht. Dauerlicht vermindert die Frequenz der Spontanaktivitat mit einem Halbwert bei 2500 lm/m2. Eine Purkinje-Verschiebung wird nicht beobachtet. Die Maxima der Spektralsensitivitat der einzelnen Pinealneurone variieren zwischen 500 und 533 mμ.

Entladungsmuster pinealer Neurone der Regenbogenforelle (Salmo irideus) bei Belichtung des Zwischenhirns

Daily rhythm of serum melatonin levels and effect of light exposure in patients with dementia of the Alzheimer's type.

A comparative study of the larval and adult pineal organs, which are sensitive to incident light, was carried out in the river lampreyLampetra japonica, using intracellular recording from the pineal photoreceptors.

Photoreception in pineal organs of larval and adult lampreys, Lampetra japonica

Locomotor activity of the river lamprey, Lampetra japonica, was investigated under a light-dark (LD 12∶12) cycle and under continuous dark conditions. Intact lampreys were entrained to the light:dark cycle. They were active mainly in the early half of the dark period and inactive in light period. The light:dark entrainment continued in 72.7% of lampreys after the removal of bilateral eyes, but additional pinealectomy made the entrainment disappear in all lampreys. When lampreys were pinealectomized with their eyes intact, light: dark entrainment was abolished in most cases. The results indicate that the pineal organ of the lamprey is a photoreceptive organ responsible for synchronizing locomotor activity to LD cycle. Under continuous dark conditions, the locomotor activity began to free-run with a period of 21.3 ± 0.9 h (mean ± SD, n = 53). This circadian rhythmicity was not affected by the removal of lateral eyes but was abolished by pinealectomy. The pineal organ appears to function as an oscillator, or as one of the oscillators, for the circadian locomotor rhythm of lampreys.

Yukitomo Morita

Papers

Daily rhythm of serum melatonin in patients with dementia of the degenerate type

Entladungsmuster pinealer Neurone der Regenbogenforelle (Salmo irideus) bei Belichtung des Zwischenhirns

Daily rhythm of serum melatonin levels and effect of light exposure in patients with dementia of the Alzheimer's type.

Photoreception in pineal organs of larval and adult lampreys, Lampetra japonica

Pineal-dependent locomotor activity of lamprey, Lampetra japonica, measured in relation to LD cycle and circadian rhythmicity