Современное состояние производства алюминия в Таджикистане

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Improved Learning and Memory in Aged Mice Deficient in Amyloid β-Degrading Neutral Endopeptidase

BACKGROUND: Neutral endopeptidase, also known as neprilysin and abbreviated NEP, is considered to be one of the key enzymes in initial human amyloid-beta (Abeta) degradation. The aim of our study was to explore the impact of NEP deficiency on the initial development of dementia-like symptoms in mice. METHODOLOGY/PRINCIPAL FINDINGS: We found that while endogenous Abeta concentrations were elevated in the brains of NEP-knockout mice at all investigated age groups, immunohistochemical analysis using monoclonal antibodies did not detect any Abeta deposits even in old NEP knockout mice. Surprisingly, tests of learning and memory revealed that the ability to learn was not reduced in old NEP-deficient mice but instead had significantly improved, and sustained learning and memory in the aged mice was congruent with improved long-term potentiation (LTP) in brain slices of the hippocampus and lateral amygdala. Our data suggests a beneficial effect of pharmacological inhibition of cerebral NEP on learning and memory in mice due to the accumulation of peptides other than Abeta degradable by NEP. By conducting degradation studies and peptide measurements in the brain of both genotypes, we identified two neuropeptide candidates, glucagon-like peptide 1 and galanin, as first potential candidates to be involved in the improved learning in aged NEP-deficient mice. CONCLUSIONS/SIGNIFICANCE: Thus, the existence of peptides targeted by NEP that improve learning and memory in older individuals may represent a promising avenue for the treatment of neurodegenerative diseases

Clinical and genetic delineation of autosomal recessive and dominant ACTL6B-related developmental brain disorders

Purpose: This study aims to comprehensively delineate the phenotypic spectrum of ACTL6B-related disorders, previously associated with both autosomal recessive and autosomal dominant neurodevelopmental disorders. Molecularly, the role of the nucleolar protein ACTL6B in contributing to the disease has remained unclear. Methods: We identified 105 affected individuals, including 39 previously reported cases, and systematically analyzed detailed clinical and genetic data for all individuals. Additionally, we conducted knockdown experiments in neuronal cells to investigate the role of ACTL6B in ribosome biogenesis. Results: Biallelic variants in ACTL6B are associated with severe-to-profound global developmental delay/intellectual disability, infantile intractable seizures, absent speech, autistic features, dystonia, and increased lethality. De novo monoallelic variants result in moderate-to-severe global developmental delay/intellectual disability, absent speech, and autistic features, whereas seizures and dystonia were less frequently observed. Dysmorphic facial features and brain abnormalities, including hypoplastic corpus callosum, and parenchymal volume loss/atrophy, are common findings in both groups. We reveal that in the nucleolus, ACTL6B plays a crucial role in ribosome biogenesis, particularly in pre-rRNA processing. Conclusion: This study provides a comprehensive characterization of the clinical spectrum of both autosomal recessive and dominant forms of ACTL6B-associated disorders. It offers a comparative analysis of their respective phenotypes provides a plausible molecular explanation and suggests their inclusion within the expanding category of “ribosomopathies.”<p/

The molecular physiology of activity-dependent bulk endocytosis of synaptic vesicles.

Central nerve terminals release neurotransmitter in response to a wide variety of stimuli. Since maintenance of neurotransmitter release is dependent on the continual supply of synaptic vesicles (SVs), nerve terminals possess an array of endocytosis modes to retrieve and recycle SV membrane and proteins. During mild stimulation conditions single SV retrieval modes such as clathrin-mediated endocytosis (CME) predominate. However during increased neuronal activity additional SV retrieval capacity is required, which is provided by activity-dependent bulk endocytosis (ADBE). ADBE is the dominant SV retrieval mechanism during elevated neuronal activity. It is a high capacity SV retrieval mode that is immediately triggered during such stimulation conditions. This review will summarise the current knowledge regarding the molecular mechanism of ADBE, including molecules required for its triggering and subsequent steps, including SV budding from bulk endosomes. The molecular relationship between ADBE and the SV reserve pool will also be discussed. It is becoming clear that an understanding of the molecular physiology of ADBE will be of critical importance in attempts to modulate both normal and abnormal synaptic function during intense neuronal activity

Metal composition of seamount encrustations from the Midpac '81 as measured by the Technical University of Claustahl

The ferromanganese crust samples studied have been taken from Central Pacific seamount areas during the research cruise Midpac 81. Two ferromanganese crust generations with different ages have been identified; in between a period of carbonate sedimentation and an episode of phosphorite formation have taken place. The older crust generation, therefore, is mostly impregnated by carbonate-apatite. Metal concentration was determined by Atomic Absorption Spectrophometry by the Technical University of Claustahl

Observation of manganese nodules and encrustations in various lakes of Finland

The limnic ferromanganese ore concretions in some Finnish lakes are described. Their chemical and mineral compositions have been measured as have their natural surroundings — the latter by means of physico-chemical in-situ analysis. The sources of the nodules' contents are discussed, and a theory based on the calculated precipitation fields of the important ore minerals is presented for the ore formation

Metal composition (wt% of dried substance) of manganese deposits from the Midpac '81 (SO18) expedition

The samples studied have been taken from the Central Pacific area during the research cruise Midpac '81. Metal concentration was determined by Atomic Absorption Spectrophometry by the Technical University of Claustahl

Chemical composition of seamount encrustations from the Midpac '81 as measured by the Bundesanstalt für Geowissenschaften und Rohstoffe (BGR)

The ferromanganese crust samples studied have been taken from Central Pacific seamount areas during the research cruise Midpac 81. Two ferromanganese crust generations with different ages have been identified; in between a period of carbonate sedimentation and an episode of phosphorite formation have taken place. The older crust generation, therefore, is mostly impregnated by carbonate-apatite. chemical concentration was determined by X-ray fluorescence (XRF) by the Geowissenschaften und Rohstoffe (BGR) on-board ship