Symmetric dimeric bisbenzimidazoles DBP(n) reduce methylation of RARB and PTEN while significantly increase methylation of rRNA genes in MCF-7 cancer cells.

Background: Hypermethylation is observed in the promoter regions of suppressor genes in the tumor cancer cells. Reactivation of these genes by demethylation of their promoters is a prospective strategy of the anticancer therapy. Previous experiments have shown that symmetric dimeric bisbenzimidazoles DBP(n) are able to block DNA methyltransferase activities.

DALMATIAN: An Algorithm for Automatic Cell Detection and Counting in 3D.

Current 3D imaging methods, including optical projection tomography, light-sheet microscopy, block-face imaging, and serial two photon tomography enable visualization of large samples of biological tissue. Large volumes of data obtained at high resolution require development of automatic image processing techniques, such as algorithms for automatic cell detection or, more generally, point-like object detection. Current approaches to automated cell detection suffer from difficulties originating from detection of particular cell types, cell populations of different brightness, non-uniformly stained, and overlapping cells.

Studying the Specific Activity of the Amide Form of HLDF-6 Peptide using the Transgenic Model of Alzheimer's Disease.

The neuroprotective and nootropic activities of the amide form (AF) of the HLDF-6 peptide (TGENHR-NH) were studied in transgenic mice of the B6C3-Tg(APPswe,PSEN1de9)85Dbo (Tg+) line (the animal model of familial Alzheimer's disease (AD)). The study was performed in 4 mouse groups: group 1 (study group): Tg+ mice intranasally injected with the peptide at a dose of 250 μg/kg; group 2 (active control): Tg+ mice intranasally injected with normal saline; group 3 (control 1): Tg- mice; and group 4 (control 2): C57Bl/6 mice. The cognitive functions were evaluated using three tests: the novel object recognition test, the conditioned passive avoidance task, and the Morris water maze.

Reconnectable fiberscopes for chronic in vivo deep-brain imaging.

Reconnectable bundles consisting of thousands of optical fibers are shown to enable high-quality image transmission, offering a platform for the creation of implantable fiberscopes for minimally invasive in vivo brain imaging. Experiments on various lines of transgenic mice verify the performance of this fiberscope as a powerful tool for chronic in vivo neuroimaging using genetically encoded calcium indicators, neuronal activity markers as well as axon growth regulators and brain-specific protein drivers in deep regions of live brain.

Green fluorescent genetically encoded calcium indicator based on calmodulin/M13-peptide from fungi.

Currently available genetically encoded calcium indicators (GECIs) utilize calmodulins (CaMs) or troponin C from metazoa such as mammals, birds, and teleosts, as calcium-binding domains. The amino acid sequences of the metazoan calcium-binding domains are highly conserved, which may limit the range of the GECI key parameters and cause undesired interactions with the intracellular environment in mammalian cells. Here we have used fungi, evolutionary distinct organisms, to derive CaM and its binding partner domains and design new GECI with improved properties.

Two-photon imaging of fiber-coupled neurons.

Optical coupling between a single, individually addressable neuron and a properly designed optical fiber is demonstrated. Two-photon imaging is shown to enable a quantitative in situ analysis of such fiber-single-neuron coupling in the live brain of transgenic mice. Fiber-optic interrogation of single pyramidal neurons in mouse brain cortex is performed with the positioning of the fiber probe relative to the neuron accurately mapped by means of two-photon imaging.

A new design for a green calcium indicator with a smaller size and a reduced number of calcium-binding sites.

Genetically encoded calcium indicators (GECIs) are mainly represented by two- or one-fluorophore-based sensors. One type of two-fluorophore-based sensor, carrying Opsanus troponin C (TnC) as the Ca-binding moiety, has two binding sites for calcium ions, providing a linear response to calcium ions. One-fluorophore-based sensors have four Ca-binding sites but are better suited for in vivo experiments.

Three-dimensional fiber-optic readout of single-neuron-resolved fluorescence in living brain of transgenic mice.

A bundle of individually addressable optical fibers is shown to enable three-dimensional optical readout from single neurons in live brain, as well as in intact brain extracted from transgenic mice. With individual fibers in the bundle being only a few microns in diameter, single neurons are readily resolved in brain images transmitted by the fiber bundle. The third dimension is added by scanning the fiber in the longitudinal direction, with the fluorescence return read out from only one of the fibers in the bundle.

Different components of conditioned food aversion memory.

Memory reconsolidation processes and protein kinase Mzeta (PKMzeta) activity in memory maintenance and reorganization are poorly understood. Therefore, we examined memory reconsolidation and PKMzeta activity during the maintenance and reorganization of a conditioned food aversion memory among snails. These processes were specifically evaluated after administration of a serotonin receptor antagonist (methiothepin), NMDA glutamate receptor antagonist (MK-801), protein synthesis inhibitor (cycloheximide; CYH), or PKMzeta inhibitor (zeta inhibitory peptide; ZIP) either 2 or 10 days after aversion training.

Comparative study of the neuroprotective and nootropic activities of the carboxylate and amide forms of the HLDF-6 peptide in animal models of Alzheimer's disease.

A comparative study of the neuroprotective and nootropic activities of two pharmaceutical substances, the HLDF-6 peptide (HLDF-6-OH) and its amide form (HLDF-6-NH2), was conducted. The study was performed in male rats using two models of a neurodegenerative disorder. Cognitive deficit in rats was induced by injection of the beta-amyloid fragment 25-35 (βA 25-35) into the giant-cell nucleus basalis of Meynert or by coinjection of βA 25-35 and ibotenic acid into the hippocampus.

Detection of Early Cancer: Genetics or Immunology? Serum Autoantibody Profiles as Markers of Malignancy.

The search for effective methods for detecting cancers at very early stages is currently a top priority of cancer research. While numerous oncogenes have been identified in and associated with human cancers, the last 50 years of molecular and genetic studies have not led to a breakthrough in either the diagnosis or the treatment of cancers. Therefore, the role of oncogenes in carcinogenesis is still unclear, as is their usefulness in the diagnosis of human cancers.

Animal Models of Depression and Drug Delivery with Food as an Effective Dosing Method: Evidences from Studies with Celecoxib and Dicholine Succinate.

Multiple models of human neuropsychiatric pathologies have been generated during the last decades which frequently use chronic dosing. Unfortunately, some drug administration methods may result in undesirable effects creating analysis confounds hampering model validity and preclinical assay outcomes. Here, automated analysis of floating behaviour, a sign of a depressive-like state, revealed that mice, subjected to a three-week intraperitoneal injection regimen, had increased floating.

The role of DNA methylation in the mechanisms of memory reconsolidation and development of amnesia.

Current considerations suggest that the mechanisms of long term memory are based on the changes of the neuronal genetic algorithms. Process of the enzyme DNA methylation have great importance to the differential genes expression, and is likely to be one of the key mechanisms of the consolidation and memory storage. The present study aimed to investigate the DNA methylation processes role in the mechanisms of the conditioned food aversion memory reconsolidation and also in the amnesia development mechanisms, caused by disturbances of the reconsolidation in Helix lucorum.

Noradrenergic and serotonergic neurochemistry arising from intranasal inoculation with α-synuclein aggregates which incite parkinsonian-like symptoms.

Alpha-synuclein (α-syn) toxic aggregates delivered by the nasal vector have been shown to modify the neurochemistry of dopamine (DA) which is associated with parkinsonian-like motor symptoms. The aim was therefore to study the intranasal effects of α-syn oligomers, fibrils or their combination on the motor behavior of aged mice in relation to possible noradrenergic and serotonergic correlates. In vitro generated α-syn oligomers and fibrils were verified using atomic force microscopy and the thioflavin T binding assay.

Adaptive maternal immune deviations as a ground for autism spectrum disorders development in children.

Autism is a vexed problem today. Overall, there is a high frequency of birth children (1:80 - 1:150) with late diagnosed autism spectrum disorders (ASD) and this trend is getting progressively stronger. The causes for the currently increased frequency of ASD and the pathogenesis of ASD are not fully understood yet.

Mice in Bion-M 1 space mission: training and selection.

After a 16-year hiatus, Russia has resumed its program of biomedical research in space, with the successful 30-day flight of the Bion-M 1 biosatellite (April 19-May 19, 2013). The principal species for biomedical research in this project was the mouse. This paper presents an overview of the scientific goals, the experimental design and the mouse training/selection program.

Stress-associated cardiovascular reaction masks heart rate dependence on physical load in mice.

When tested on the treadmill mice do not display a graded increase of heart rate (HR), but rather a sharp shift of cardiovascular indices to high levels at the onset of locomotion. We hypothesized that under test conditions cardiovascular reaction to physical load in mice is masked with stress-associated HR increase. To test this hypothesis we monitored mean arterial pressure (MAP) and heart rate in C57BL/6 mice after exposure to stressful stimuli, during spontaneous locomotion in the open-field test, treadmill running or running in a wheel installed in the home cage.

Intranasal administration of alpha-synuclein aggregates: a Parkinson's disease model with behavioral and neurochemical correlates.

Parkinson's disease (PD) is a neurodegenerative disorder in which both alpha-synuclein (α-syn) and dopamine (DA) have a critical role. Our previous studies instigated a novel PD model based on nasal inoculation with α-syn aggregates which expressed parkinsonian-like behavioral and immunological features. The current study in mice substantiated the robustness of the amyloid nasal vector model by examining behavioral consequences with respect to DA-ergic neurochemical corollaries.

Open field behavior and the state of the thymus and adrenal glands in rats after exposure to stress and elevation of blood level of autoantibodies to dopamine and glutamate.

Blood level of autoantibodies to dopamine and glutamate in rats increased in 4 weeks after exposure to stress. Under these conditions, active animals demonstrated decreased motor and exploratory activity in the open field, while in passive animals, only the number of explored objects decreased. The increase in blood level of autoantibodies to dopamine and glutamate in rats exposed to stress was followed by an increase in the adrenal gland weight in active animals and thymus weight in passive animals.

Long-distance effects of human subjective status on the blood physicochemical characteristics.

The external long-distance manifestations of the subjective status of a human being are analyzed. The subjective states of a human being can be objectively recorded at a long distance. A contact-free long-distance effect of human subjective status on the physicochemical parameters of the blood is demonstrated.

Effects of prenatal exposure to antibodies against brain-specific anion transporter on cognitive functions in rats.

We studied the effects of single intravenous injection of antibodies to brain-specific transmembrane anion transporter (BSAT1; 5 mg/kg) to pregnant rats (gestation day 10) on cognitive functions and behavior of their progeny. One of major functions of BSAT1 (or Oatp1c1) is specific transport of thyroxin across the blood-brain barrier. Female rats of two control groups were injected with non-specific Ig and 0.

Cytokine levels in rat blood and brain structures after administration of lipopolysaccharide.

We compared cytokine profile of rat serum and brain structures after immune status modulation by LPS (30 μg/kg intraperitoneally). The content of inflammatory (IL-1α, IL-1β, IL-2, IL-6, IFN-γ, and TNF-α) and anti-inflammatory (IL-4 and IL-10) cytokines in biological samples of animals was measured on days 1 and 7 after antigenic stimulation. LPS administration reduced the levels of both inflammatory and anti-inflammatory cytokines in the peripheral blood of the rats, especially on the 1st day.

Contrasting of biological samples for X-ray synchrotron microtomography.

The method of contrasting with iodine ions was developed to obtain high-resolution 3D images of large biological specimens using a synchrotron X-ray microtomography unit. It was shown that the samples (late mouse embryos) treated with 50% Lugol solution with addition of 25% ethanol for 48 h followed by a 48-h washout in phosphate buffered saline had maximum contrast and lowest compression artifacts. Processing of samples by this protocol allowed detecting zones of active proliferation.

Estimation of the level of anxiety in rats: differences in results of open-field test, elevated plus-maze test, and Vogel's conflict test.

We compared individual anxiety assessed by three standard tests, open-field test, elevated plus-maze test, and Vogel conflict drinking test, in the same animals. No significant correlations between the main anxiety parameters were found in these three experimental models. Groups of animals with high and low anxiety rats were formed by a single parameter and subsequent selection of two extreme groups (10%).

Distinct functional brain regional integration of Casp3, Ascl1 and S100a6 gene expression in spatial memory.

Evaluating the brain structural expression of defined genes involved in basic biological processes of neurogenesis, apoptosis or neural plasticity may facilitate the understanding of genetic mechanisms underlying spatial memory. The aim of the present study was to compare Ascl1, Casp3 and S100a6 gene expression in the hippocampus, prefrontal cortex and cerebellum of adult rats in water maze spatial memory performance. After four days training, the mean platform time (<10s) was evidence of stable long-term spatial memory formation.