The Role of Neurotransmitters and Proteins in the Genetic-Functional Organization of the Animal Brain

It was shown that animals that differ in behavioral characteristics (August and Wistar rats) also differ in neurotransmitter and protein metabolism, which can be considered as tests that adequately reflect the functional condition of the central nervous system. These differences are expressed at the level of both subcortical structures (the hippocampus and caudate nucleus) and various morphofunctional types of the sensorimotor cortex neurons (layers III and V). Studies on genetically different animals strains have revealed metabolic features that allow the determination of individual behavioral features and an estimation of individual brain structures in these processes.     

Type 4 pili are dispensable for biofilm development in the cyanobacterium Synechococcus elongatus

The hair‐like cell appendages denoted as type IV pili are crucial for biofilm formation in diverse eubacteria. The protein complex responsible for type IV pilus assembly is homologous with the type II protein secretion complex. In the cyanobacterium Synechococcus elongatus PCC 7942, the gene Synpcc7942_2071 encodes an ATPase homologue of type II/type IV systems. Here, we report that inactivation of Synpcc7942_2071 strongly affected the suite of proteins present in the extracellular milieu (exo‐proteome) and eliminated pili observable by electron microscopy. These results support a role for this gene product in protein secretion as well as in pili formation. As we previously reported, inactivation of Synpcc7942_2071 enables biofilm formation and suppresses the planktonic growth of S. elongatus. Thus, pili are dispensable for biofilm development in this cyanobacterium, in contrast to their biofilm‐promoting function in type IV pili‐producing heterotrophic bacteria. Nevertheless, pili removal is not required for biofilm formation as evident by a piliated mutant of S. elongatus that develops biofilms. We show that adhesion and timing of biofilm development differ between the piliated and non‐piliated strains. The study demonstrates key differences in the process of biofilm formation between cyanobacteria and well‐studied type IV pili‐producing heterotrophic bacteria.     

Signaling Pathways That Control the Growth and Survival of Prostate Carcinoma Cells in the Absence of Androgens

Androgen-dependent human prostate adenocarcinoma cell line LNCaP was used to study the effect of androgen deprivation on the cell response to TNF-related cytokines. Several signaling pathways were implicated in cell survival in the absence of androgens. In androgen-deprived LNCaP cells, TNF- and TRAIL stimulated the cell growth and activated the mitogenic and antiapoptotic signaling pathways involving NF-B, STAT3, PI3K, and -catenin. The results suggested a role of cytokines in the survival of prostate adenocarcinoma cells deprived of androgens in vitro.     

The role of phosphatidylinositol 3-kinase in the regulation of cell response to steroid hormones.

Phosphatidylinositol 3-kinase (PI-3 kinase) has been implicated in the regulation of many cellular processes, including growth and transformation. We describe the effect of glucocorticoids on cell growth, phosphoinositide formation and PI-3 kinase activity in Rous sarcoma virus-transformed hamster fibroblasts (HET-SR). Using a prolonged dexamethasone treatment of HET-SR cells we have selected a new glucocorticoid receptor-positive cell subline, HET-SR(h), that was resistant to growth inhibitory action of dexamethasone and/or non-hormonal drugs (vinblastine, adriamycin) and was characterized by higher levels of phosphoinositide formation and increased PI-3 kinase activity. Study of the short-term hormone action has shown that both dexamethasone-sensitive and -resistant sublines responded to hormone by a decrease in phospholipid turnover rate. At the same time, in both cell lines activation of PI-3 kinase after dexamethasone addition was revealed. Dexamethasone-dependent activation of PI-3 kinase was more significant and maintained for a longer period in HET-SR(h) cells than in parent HET-SR cells. Finally, by transfecting p110*, a constitutively active catalytic subunit of PI-3 kinase, into hormone-sensitive HET-SR cells, we have found a marked increase in cell resistance to growth inhibitory dexamethasone action. These results suggest that PI-3 kinase may serve as one of the factors providing cell resistance to cytostatic drugs.     

Regulation by Delta-Sleep-Inducing Peptide of the Neurochemical Changes in the Brain Associated with Dopaminergic System Hyperactivity

The influence of a single injection of delta-sleep-inducing peptide (DSIP; 30 g/kg body weight) on neurochemical parameters of rats' brain was studied under the conditions of chronic administration of dopamine analogs inducing DA-system hyperactivity – 50 mg/kg body weight of L-DOPA for 30 days or 2,5 mg/kg body weight of amphetamine for 21 days. The parameters of serotonergic system (MAO A activity, 5-HT, and 5-HIAA contents) and of dopaminergic system (MAO B activity, DA, NA, and HVA contents) were investigated in the cortex and caudate nucleus of control, DA or amphetamine, and DSIP receiving rats. Changes caused by the two DA-system activating drugs had both similarities and differences, and the corrective action of DSIP also had certain peculiarities depending on the pharmacological preparation used for the induction of DA-system hyperactivity and on the investigated brain structure. It is supposed that DSIP action might be based on the activation of serotonergic system that ensures the adaptive behavior of the animals.     

Phosphorylated Akt1 in human breast cancer measured by direct sandwich enzyme-linked immunosorbent assay: Correlation with clinicopathological features and tumor VEGF-signaling system component levels

Protein kinase B (Akt) plays a major role in the regulation of breast cancer growth, survival, hormone, drug and radiosensitivity, but the clinical value of its expression and activation in human tumors is unclear. Activated Akt1 (pAkt1) expression was quantified in a series of 46 breast cancer and adjacent mammary gland samples by a direct Path-Scan PhosphoAkt1 (Ser473) sandwich ELISA kit. VEGF, sVEGFR1 and sVEGFR2 levels were measured simultaneously by standard ELISA kits. Forty-nine percent of the tumors had an increased pAkt1 level as compared to adjacent tissue. pAkt1 levels were significantly higher in stage IIb than in stage I-IIa tumors. The frequency of pAkt1 elevation was positively associated with tumor size and malignancy grade. pAkt1 was also twice as frequently increased in PgR-negative as in PgR-positive tumors, while its mean level was significantly higher in ER-positive than in ER-negative tumors. VEGF, sVEGFR1 and sVEGFR2 were increased in 73-85% of the tumors, but no associations with most clinicobiological factors and pAkt1 level were found. In conclusion, activation of Akt1 is not associated with VEGF signaling protein expression in breast cancer but is related to tumor size, grade of malignancy, and steroid receptor status.     

Novel miRNAs as Potential Regulators of PD-1/PD-L1 Immune Checkpoint,and Prognostic Value of MIR9-1 and MIR124-2 Methylation in Ovarian Cancer

Molecular Biology - Ovarian cancer (OC) is mostly detected at late stages weighed down with metastasis, and the five-year survival rate of patients is only 30%, which dictates the necessity to...