Genetic Association between Alzheimer’s Disease Risk Variant of the <Emphasis Type="Italic">PICALM</Emphasis> Gene and Auditory Event-Related Potentials in Aging

Aging and genetic predisposition are major risk factors in age-related neurodegenerative disorders. The most common neurodegenerative disorder is Alzheimer’s disease (AD). Genome-wide association studies (GWAS) have identified statistically significant association of the PICALM rs3851179 polymorphism with AD. The PICALM G allele increases the risk of AD, while the A allele has a protective effect. We examined the association of the PICALM rs3851179 polymorphism with parameters of the P3 component of auditory event-related potentials (ERPs) in 87 non-demented volunteers (age, 19–77 years) subdivided into two cohorts younger and older than 50 years of age. We found statistically significant association between the AD risk variant PICALM GG and increase in the P3 latency in subjects over 50 years old. The age-dependent increase in the P3 latency was more pronounced in the PICALM GG carriers than in the carriers of the PICALM AA and PICALM AG genotypes. The observed PICALM-associated changes in the neurophysiological processes indicate a decline in the information processing speed with aging due, probably, to neuronal dysfunction and subclinical neurodegeneration of the neuronal networks in the hippocampus and the frontal and parietal cortical areas. Such changes were less pronounced in the carriers of the PICALM gene A allele, which might explain the protective effect of this allele in the cognitive decline and AD development.     

The effect of functional overstrain of the central nervous system and endocrine disorders on the development of experimental atherosclerosis in dogs]

In a chronic experiment (up to 6 years) on dogs (13) a protracted functional overstrain of the CNS was associated with an additional action changing the hormonal background (castration and mercasolyl injection). A steady hypercholesteremia, atherosclerotic changes in different intraorganic arteries, particularly in the myocardium, developed in dogs; dystrophic processes occurred in the parenchyma of various organs. An important role of functional overstrain of the CNS as one of the leading factors of the "risk" determining the development of disturbances of the regulation of lipid metabolism and formation of the atherosclerotic process in the vessels was demonstrated.     

Two types of binocular convergence of visual information in the cat superior colliculus

During binocular stimulation of different sectors of the retina the amplitude of the two first postsynaptic components of the evoked potential in the superior colliculus to the second stimulus varies with the time delay between the testing and conditioning stimuli. Correlation is shown between the form of the evoked potential arising in response to the conditioning stimulus and the character of convergence of visual impluses in the superior colliculus. Qualitative differences are found in binocular interaction between sensory impulses depending on the way in which the conditioning impulses reach the region of the superior colliculus tested. An attempt is made to assess interaction between sensory volleys in the superior colliculus quantitatively.Institute of the Brain, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 5, No. 2, pp. 133–137, March–April, 1973.     

Transport of colloidal particles in lymphatics and vasculature after subcutaneous injection.

This study was designed to determine the transport of subcutaneously injected viral-size colloid particles into the lymph and the vascular system in the hind leg of the dog. Transport of two colloid particles, with average size approximately 1 and 0.41 microm, respectively, and with and without leg rotation, was tested. Leg rotation serves to enhance the lymph flow rates. The right femoral vein, lymph vessel, and left femoral artery were cannulated while the animal was under anesthesia, and samples were collected at regular intervals after subcutaneous injection of the particles at the right knee level. The number of particles in the samples were counted under fluorescence microscopy by using a hemocytometer. With and without leg rotation, both particle sets were rapidly taken up into the venous blood and into the lymph fluid. The number of particles carried away from the injection site within the first 5 min was <5% of the injected pool. Particles were also seen in arterial blood samples; this suggests reflow and a prolonged residence time in the blood. These results show that particles the size of viruses are rapidly taken up into the lymphatics and blood vessels after subcutaneous deposition.     

Morphological and molecular investigations of Paramecium schewiakoffi sp. nov. (Ciliophora, Oligohymenophorea) and current status of distribution and taxonomy of Paramecium spp.

Paramecium schewiakoffi sp. nov. is described from a pond in Shanghai, China. It is a freshwater species belonging to the “aurelia” subgroup of the genus. It is of similar size and shape to P. jenningsi, but has a single large micronucleus of the “chromosomal” morphological type, while P. jenningsi has two smaller micronuclei. The general morphology, morphometric characteristics and nuclear reorganization pattern, a random amplified polymorphic DNA (RAPD) fingerprint pattern, and the small subunit rRNA gene sequence are presented for the species. Comparison of P. schewiakoffi with the other species of Paramecium indicates that it is a valid new species of the genus. Geographical locations reported for many Paramecium species do not support the theory that all ciliates have a cosmopolitan distribution. It is proposed that, in an extension of Jankowski's earlier suggestion, the genus Paramecium should be subdivided into four subgenera: Chloroparamecium, Helianter, Cypriostomum and Paramecium, on the basis of morphometric, biological and molecular differences.     

Ste20-like protein kinase SLK (LOSK) regulates microtubule organization by targeting dynactin to the centrosome

The microtubule- and centrosome-associated Ste20-like kinase (SLK; long Ste20-like kinase [LOSK]) regulates cytoskeleton organization and cell polarization and spreading. Its inhibition causes microtubule disorganization and release of centrosomal dynactin. The major function of dynactin is minus end–directed transport along microtubules in a complex with dynein motor. In addition, dynactin is required for maintenance of the microtubule radial array in interphase cells, and depletion of its centrosomal pool entails microtubule disorganization. Here we demonstrate that SLK (LOSK) phosphorylates the p150^Glued subunit of dynactin and thus targets it to the centrosome, where it maintains microtubule radial organization. We show that phosphorylation is required only for centrosomal localization of p150^Glued and does not affect its microtubule-organizing properties: artificial targeting of nonphosphorylatable p150^Glued to the centrosome restores microtubule radial array in cells with inhibited SLK (LOSK). The phosphorylation site is located in a microtubule-binding region that is variable for two isoforms (1A and 1B) of p150^Glued expressed in cultured fibroblast-like cells (isoform 1B lacks 20 amino acids in the basic microtubule-binding domain). The fact that SLK (LOSK) phosphorylates only a minor isoform 1A of p150^Glued suggests that transport and microtubule-organizing functions of dynactin are distinctly divided between the two isoforms. We also show that dynactin phosphorylation is involved in Golgi reorientation in polarized cells.     

Microsatellite cross-species amplification in the genus Littorina and detection of null alleles in Littorina saxatilis

Microsatellite DNA is widely used as population genetic marker,but the cost of using microsatellites is high, as they usuallyneed to be developed and optimized for each species separately.Cross-species amplification of microsatellites is thereforecommonly applied to bring down the cost, but it can also involvegenotyping errors. We studied cross-species amplification ofmicrosatellites in four species of the Atlantic group of Littorina(Neritrema): L. saxatilis (Olivi, 1792), L. obtusata (Linnaeus,1758), L. fabalis (Turton, 1825) and L. arcana Hannaford Ellis,1978 to investigate whether markers originally developed fora more distantly related Pacific species [L. subrotundata (Carpenter,1864)] suffered from more amplification problems than markersdeveloped for one of the species in the Atlantic group (L. saxatilis).We also compared variation in amplification success among thespecies and among different regions in the NE Atlantic. Approximatelyhalf of the 12 primers developed for L. subrotundata and theseven primers developed for L. saxatilis were successfully amplifiedin other species of the subgenus. The success was dependenton phylogenetic distance among species within the subgenus.On the other hand, the variation in performance of the locibetween geographically remote populations of the same specieswas as high as variation among the species. In earlier studiesstatistical analyses indicated that several loci showed a heterozygotedeficiency due to null alleles. The presence of null alleleswas confirmed by a segregation analysis of the microsatelliteloci in eight half-sib families of L. saxatilis. (Received 2 April 2007; accepted 19 November 2007)     

Physical criteria of pathological processes. I. Change in the functional hemispheric asymmetry at various stages of rheumatic diseases]

The functional interhemispheric asymmetry of brain in patients with systemic rheumatic diseases was estimated by measuring brain direct current potentials. It is shown that different types of functional interhemispheric asymmetry correspond to different stages of systemic rheumatic diseases. At early stages, the left hemisphere asymmetry dominates, at expressed stages, the right hemisphere asymmetry is prevalent, and the terminal stage is characterized by the loss of functional interhemispheric asymmetry.