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PubMed2025

The Effect of APOE ε4 Allele on Dynamic Local Spontaneous Brain Activity and Functional Integration in Alzheimer's Disease.

The apolipoprotein E (APOE) ε4 allele is the most important genetic risk factor for sporadic Alzheimer's disease (AD), yet its mechanisms in AD pathology and cognitive decline remain unclear. Using a sliding-time window approach to directly quantify the instantaneous fluctuations of various local metrics based on continuous time series and calculate voxel-wise concordance of these metrics, we explored the impact of APOE ε4 on dynamic local brain activity and functional integration in AD, and its interrelations with plasma biomarkers and cognition. Results showed that APOE ε4 widely affected dALFF, dReHo, dGSCorr, and voxel-wise concordance. For AD patients, APOE ε4 carriers uniquely exhibited correlations between dALFF in the right angular gyrus/supramarginal gyrus and MoCA scores and orientation function, and between voxel-wise concordance in the right caudate nucleus (CAU) and general cognition, attention, language function, orientation function, plasma Aβ42. Critically, APOE ε4-related altered voxel-wise concordance in the right CAU mediated the relationship between plasma Aβ and language cognition in AD. Moreover, the combined model incorporating dynamic metrics, plasma AD biomarkers, and demographic data effectively distinguished AD from NC (AUC = 0.94, sensitivity = 87.69%, specificity = 86.84%). In conclusion, the APOE ε4 allele might play a pivotal role in modulating brain dynamic functional activities in AD, which may contribute to the association between Aβ pathology and cognitive decline. Our findings may provide imaging markers and targets for the diagnosis and treatment of AD.

Humans↗
PubMed1979

Afferent sympathetic unmyelinated fibres with left ventricular endings in cats.

1. We recorded the electrical impulse activity of thirty-three single afferent fibres with left ventricular endings from the third and fourth left thoracic sympathetic rami communicantes of anaesthetized cats. Their conduction velocity ranged from 0.23 to 0.98 m/sec (group C). 2. The endings of each fibre were localized to the left ventricle by mechanical probing performed at the end of the experiment on the non-beating heart. No fibre had multiple sensory fields. 3. The impulse activity (0.95 +/- 0.2 impulses/sec) was spontaneous but most often a fixed temporal correlation between impulses and ventricular dynamics was not detectable. It was increased during occlusion of the thoracic aorta, I.V. administration of isoprenaline or infusion of saline. It was unaffected by asphyxia, haemorrhage and I.V. administration of acetylcholine. It was decreased during occlusion of inferior vena cava. Therefore these ventricular receptors appeared to be mainly sensitive to mechanical events. 4. The fibres were excited during the occlusion of the left main coronary artery, after a latency of 14.5 +/- 1.3 sec. They were also excited during ventricular fibrillation, exhibiting the highest values of impulse activity (2.51 +/- 0.4 impulses/sec). The increase in impulse activity during ventricular fibrillation was sometimes immediate and extreme, with peak frequencies of about 50 impulses/sec. 5. These spontaneously active ventricular receptors with unmyelinated nerve fibres participate in the transmission of the continuous impulse activity which from the cardiovascular system reaches the spinal cord through the sympathetic nerves and which is likely to contribute to the neural control of circulation. Thus the unmyelinated cardiac sympathetic afferents should not be considered as purely nociceptive in function.

Action Potentials↗
PubMed1979

[Immune reactions in assessing the disease prognosis in soft tissue sarcomas].

Under examination were 60 patients with local forms of soft tissue sarcomas of various histological structure. By means of skin delayed hypersensitivity test for dinitrochlorobenzene (DNCB) and tuberculin as well as cell immunity reaction in vitro the immune response was shown to be of value in estimating the prognosis of the disease. The dynamics of immune reactions 2-3 months following the operation proved to be of greatest prognostic value. Among the employed immunological tests the skin test for DNCB and the reaction of spontaneous rosette-forming provided the most comprehensive information as to the control over the clinical course of malignant lesion.

Adolescent↗
PubMed1977

Intracellular crystal-bearing vesicles in the epidermis of scleractinian corals, Astrangia danae (Agassiz) and Porites porites (Pallas).

Orthorhombic aragonitic crystals, embedded with a granular lipo-protein matrix and surrounded by a trilaminar membrane, are localized in the apical cytoplasm of epidermal cells of Scleractinian corals. Adult specimens of Astrangia danae (Agassiz) and settled planulae of Porites porites (Pallas) contain crystals averaging 0.7 mu by 0.1 mu by 0.3 mu within Golgi-derived vesicles. Short-term labelling with 45Ca reveals distribution of radioactivity amont a basic tissue fraction (92%) an acid tissue fraction (5%) and a skeletal fraction (3%). Identification of the primordial crystal population within membrane-bound visicles provides overwhelming evidence for the intracellular mode of calcification in Scleractinia. Moreover, it permits development of a novel concept of cellular regulation over these dynamic events. The membrane-bound vesicel is a miniature crystal fabrication station and a vehicle responsible for transportation of seed crystals and an organic matrix material to sites of discharge from the cell. The vesicle membrane becomes a probable locus of active transport and enzymatic activity as well as a physical barrier to be penetrated for release of vesicle contents into the extracellular milieu. Contact between the vesicle membrane and the plasmalemma would result in exocytosis and the onset of skeletogenesis. Principles governing crystal growth would prevail from then on. The released crystal becomes a nucleation catalyst and the organic matrix, a supply of ionic calcium for self-limiting crystallization. Crystals are produced by the organism spontaneously and continuously from shortly after larval attachment throughout the life of the polyp. Therefore, these membrane-bound vesicles signal the dynamic process by which initiation, differentiation, growth and limitation of the coral skeleton is regulated.

Animals↗
PubMed1977

[The comparison of human reflex and instinct behaviour (author's transl)].

On the basis of characteristics of the exteroceptive reflexes and of the instincts it was shown that instinct behaviour developed from reflex characteristics (local characteristic of the stimuli, pos. and neg. taxis, habituation, conditioning). Most similarities are found between reflex and avoidance instinct behaviour (instincts for excretion, thermoregulation, body care, pain avoidance and safety). Except the safety instinct, all others react on stimuli, characterised by the localisation of the receptors. In the safety instinct the structure of the stimulus becomes important, together with the growing importance of the third dimension. This instinct shows also for the first time a variability of the threshold with spontaneous remaining low for some time after stimulation of the system. Inverse the gain instincts (nutrition, sex and social instinct). Here the threshold falls spontaneously, when stimuli are lacking and raises, when stimuli are found. The spontaneous motor expression of the lowering of the threshold is the appetite behaviour. It means seeking stimuli, which will be gained by elements of the initial and terminal success behaviour. The successfull nutritional and sexual behaviour is stopped by success inhibition, whereas the social instinct remains in the terminal success behaviour with group dynamic hierarchy, with imitating and helping behaviour. Overchanging of the gain instincts provokes avoidance behaviour with constant threshold. The neural systems of most reflexes lie distributed in the spinal cord and brainstem, the ones of the instincts in the limbic part of the brain, the nutrition and sex instinct with a hypothalamic pacemaker. Simultaneous activation of two or many instinct motivation systems result, not comparable with the direct reflex interaction, in interactions on the level of the global interaction, in interactions on the level of the global integration (summation, mixture, synthesis, rest, oscillation, intention) which projects the activity patterns via the motor cortex to the peripheral neurons. There it is completed by the reflexes. The hormonal and vegetative projection instead go directly to the end organs. The motivation is responsible for the subjective experience, the dominating integration with its motor projection for the instinct behaviour.

Behavior↗