Screening for Asymptomatic Urinary Retention in Older Adult Men at Admission to the Internal Medicine Department: A Prospective Study.

Background: Screening for asymptomatic urinary retention (AUR) in older adult men at hospital admission to the internal medicine department has never been studied.

Objectives: To assess the incidence of AUR in older adult men at hospital admission, its risk factors, and its outcome.

Methods: The study comprised 111 older adult men aged ≥ 75 years who were admitted to three internal medicine departments.

[Prion Properties of Alpha-Synuclein].

The prion properties of alpha-synuclein, a key aggregating protein involved in the pathogenesis of so-called synucleinopathies, including Parkinson's disease (PD), dementia with Lewy bodies, multiple system atrophy, and its various conformers are discussed. It is shown that alpha-synuclein may be transferred between cells by prion-like propagation. Similarly to other prions, alpha-synuclein aggregation develops from the initial lag-phase (nucleation) to the subsequent growth phase (elongation), and to the stationary phase where the aggregates and monomers exist in equilibrium.

[Transmission of pathogenic protein aggregates in Alzheimer's disease].

Deposits of amyloid peptide Aβ and intracellular aggregates of hyperphosphorylated tau protein in the brain of patients are major neuropathological features of Alzheimer's disease (AD). For a long time, the possibility of horizontal transmission of Aβ aggregates from cell to cell and from person to person remained hypothetical, since there was no experimental evidence. However, in 1993, the formation of senile plaques was confirmed in the brains of animals after intracerebral injections of AD patient brain homogenates or homogenates of the brain of transgenic mice enriched with Aβ aggregates.

[Role of the ABC transporters A1 and G1, key reverse cholesterol transport proteins, in atherosclerosis].

Atherosclerosis is one of the most common causes of death worldwide. Epidemiology studies firmly established an inverse relationship between atherogenesis and distorted lipid metabolism, in particular, higher levels of total cholesterol, an accumulation of CH-laden macrophages (foam cells), and lower plasma levels of antiatherogenic high density lipoprotein (HDL). It is believed that the reverse cholesterol transport, a process that removes excess cholesterol from peripheral tissues/cells including macrophages to circulating HDL, is one of the main mechanisms responsible for anti-atherogenic properties of HDL.

Expression of human amyloid precursor protein in Drosophila melanogaster nerve cells causes a decrease in presynaptic gene mRNA levels.

Amyloid precursor protein (APP) is a key player in Alzheimer's disease. The proteolytic cleavage of APP results in various short peptide fragments including the toxic amyloid-beta peptide, which is a main component of senile plaques. However, the functions of APP and its processed fragments are not yet well understood.

Dendrimer D5 is a vector for peptide transport to brain cells.

Dendrimers are a new class of nonviral vectors for gene or drug transport. Dendrimer capacity to penetrate through the blood-brain barrier remaines little studied. Biotinylated polylysine dendrimer D5, similarly to human growth hormone biotinylated fragment covalently bound to D5 dendrimer, penetrates through the blood-brain barrier and accumulates in Drosophila brain after injection into the abdomen.

Reduced content of α-synuclein in peripheral blood leukocytes of patients with LRRK2-associated Parkinson's disease.

Measurement of α-synuclein level in the peripheral blood was proposed as a diagnostic test for Parkinson's disease. However, the results of these studies remain contradictory, probably because the examined samples included patients with different etiology of Parkinson's disease. To verify this assumption we studied the levels of α-synuclein in peripheral blood leukocytes of patients with Parkinson's disease associated with mutations in the gene of leucine-rich kinase 2 (LRRK2).

The role of the cantilever in Kelvin probe force microscopy measurements.

The role of the cantilever in quantitative Kelvin probe force microscopy (KPFM) is rigorously analyzed. We use the boundary element method to calculate the point spread function of the measuring probe: Tip and cantilever. The calculations show that the cantilever has a very strong effect on the absolute value of the measured contact potential difference even under ultra-high vacuum conditions, and we demonstrate a good agreement between our model and KPFM measurements in ultra-high vacuum of NaCl monolayers grown on Cu(111).

Apolipoprotein E-mimetics inhibit neurodegeneration and restore cognitive functions in a transgenic Drosophila model of Alzheimer's disease.

Background: Mutations of the amyloid precursor protein gene (APP) are found in familial forms of Alzheimer's disease (AD) and some lead to the elevated production of amyloid-beta-protein (Abeta). While Abeta has been implicated in the causation of AD, the exact role played by Abeta and its APP precursor are still unclear.

Principal Findings: In our study, Drosophila melanogaster transgenics were established as a model to analyze AD-like pathology caused by APP overexpression.

High level of alpha-synuclein mRNA in peripheral lymphocytes of patients with alcohol dependence syndrome.

The content of mRNA for alpha-synuclein (a key protein of the dopaminergic system) was elevated in the peripheral lymphocytes of patients with alcohol dependence syndrome. Increased level of alpha-synuclein mRNA was not associated with changes in the expression of NR4A2 gene encoding Nurrl, one of the main transcription factors of dopaminergic neurons.

Screening for LRRK2 mutations in patients with Parkinson's disease in Russia: identification of a novel LRRK2 variant.

Background And Purpose: Mutations in LRRK2, encoding leucine-rich repeat kinase 2 (or Dardarin), cause autosomal dominant Parkinson's disease (AdPD) and are also found in sporadic PD (sPD). To investigate the frequency of LRRK2 mutations in a sample of Russian PD patients.

Methods: We sequenced the complete coding region of LRRK2 in 65 patients with AdPD and in 30 patients with sPD.

Selection of peptides binding to the amyloid b-protein reveals potential inhibitors of amyloid formation.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by extracellular amyloid plaques, cerebrovascular amyloid deposits, intracellular neurofibrillary tangles, and neuronal loss. Amyloid deposits are composed of insoluble fibers of a 39-43 amino acid peptide named the amyloid beta-protein (A beta). Neuropathological and genetic studies provide strong evidence of a key role for A beta amyloidosis in the pathogenesis of AD.

PS1 activates PI3K thus inhibiting GSK-3 activity and tau overphosphorylation: effects of FAD mutations.

Phosphatidylinositol 3-kinase (PI3K) promotes cell survival and communication by activating its downstream effector Akt kinase. Here we show that PS1, a protein involved in familial Alzheimer's disease (FAD), promotes cell survival by activating the PI3K/Akt cell survival signaling. This function of PS1 is unaffected by gamma-secretase inhibitors.

Amyloidogenic and anti-amyloidogenic properties of recombinant transthyretin variants.

Most transthyretin (TTR) mutations lead to TTR amyloid depositions in patients with familial amyloidotic polyneuropathy and familial amyloidotic cardiomyopathy. However, though an amyloidogenic protein itself, TTR inhibits aggregation of Alzheimer's amyloid beta protein (A beta) in vitro and in vivo. The pathogenic relationship between two amyloidogenic processes remains unclear.

Cdc2 phosphorylation of nucleolin demarcates mitotic stages and Alzheimer's disease pathology.

Nucleolin is a major multifunctional nuclear phosphoprotein that is phosphorylated by Cdc2 kinase in mitosis and that participates in a number of cellular processes. The monoclonal antibody TG-3 generated against neurofibrillary tangles (NFT) found in Alzheimer's disease (AD) is highly specific for mitotic cells in culture. We here demonstrate that phosphorylation of nucleolin by Cdc2 kinase generates the TG-3 epitope.

The role of Alzheimer's disease-related presenilin 1 in intercellular adhesion.

Most cases of familial early-onset Alzheimer's disease are caused by mutations in the presenilin 1 (PS1) gene. However, the cellular functions of PS1 are unknown. We showed predominant localization of PS1 to cell-cell contacts of the plasma membrane in human prostate epithelial tissue and in a human epithelial cell line HEp2 stably transfected with an inducible PS1 construct.

Endogenous presenilin 1 redistributes to the surface of lamellipodia upon adhesion of Jurkat cells to a collagen matrix.

Most familial early-onset Alzheimer's disease cases are caused by mutations in the presenilin 1 (PS1) gene. Subcellular localization of the endogenous PS1 is essential for understanding its function, interactions with proteins, and role in Alzheimer's disease. Although numerous studies revealed predominant localization of PS1 to endoplasmic reticulum and Golgi, there are conflicting reports on the localization of PS1 to the cell surface.

Interaction of transthyretin with amyloid beta-protein: binding and inhibition of amyloid formation.

Aggregated amyloid beta-protein (A beta) is a key component of the amyloid depositions found in the brains of patients with Alzheimer's disease. In contrast, in cerebrospinal fluid (CSF), A beta is found in a soluble form. The analysis of complexes of A beta with CSF proteins in a KBr gradient revealed an association of A beta only with free proteins and not with lipoprotein particles.

USF binds to the APB alpha sequence in the promoter of the amyloid beta-protein precursor gene.

The APB alpha domain in the amyloid beta-protein precursor (APP) promoter contains a nuclear factor binding domain with the core recognition sequence TCAGCT-GAC. Proteins in nuclear extracts from brain and numerous cell lines bind to this domain and it contributes approximately 10-30% to the basal APP promoter activity. Included in this domain is the CANNTG motif, which is recognized by basic helix-loop-helix transcription factors.

Transthyretin sequesters amyloid beta protein and prevents amyloid formation.

The cardinal pathological features of Alzheimer disease are depositions of aggregated amyloid beta protein (A beta) in the brain and cerebrovasculature. However, the A beta is found in a soluble form in cerebrospinal fluid in healthy individuals and patients with Alzheimer disease. We postulate that sequestration of A beta precludes amyloid formation.

Ceruloplasmin gene defect associated with epilepsy in EL mice.

Epilepsy is a dominant trait in EL mice, a model for human complex partial seizures. We recently mapped the major gene, El-1, to chromosome 9 near the predicted location for the ceruloplasmin (Cp) gene. We now present evidence for a partial duplication in the Cp gene in EL mice.