Blood Morphology and Hematology of Adult Baikal Seals ( Gmelin, 1788) Under Professional Care.

Studying the blood cell morphology of marine mammals provides an opportunity to elucidate the physiological mechanisms of adaptive changes associated with the aquatic habitat that occur at the cellular level, as well as adaptations to changing environmental conditions and under various physiological and pathological processes. The Baikal seal [ (family Phocidae)] is endemic to the freshwater Lake Baikal, but comprehensive hematology data are not available. We studied the morphological features of blood cells of twelve clinically normal, adult Baikal seals ( = 6 males, = 6 females) from two oceanariums under professional care for eight years.

mTOR pathway occupies a central role in the emergence of latent cancer cells.

The current focus in oncology research is the translational control of cancer cells as a major mechanism of cellular plasticity. Recent evidence has prompted a reevaluation of the role of the mTOR pathway in cancer development leading to new conclusions. The mechanistic mTOR inhibition is well known to be a tool for generating quiescent stem cells and cancer cells.

Macrophage and microglia polarization: focus on autophagy-dependent reprogramming.

The approach to the study of autophagy has been undergoing considerable change lately: from investigations of the protein components of autophagic machinery to its regulation at different molecular levels. Autophagy is being examinated not only as a separated degradative process in cells but as an executor mechanism of certain signaling pathways that converge on it, being activated under specific conditions. Additionally, autophagy is beginning to be observed as a key integral part of cellular reprogramming, the transition from one phenotypic state to another associated with rapid degradation of the previous proteostasis.

The mTOR Pathway in Pluripotent Stem Cells: Lessons for Understanding Cancer Cell Dormancy.

Currently, the success of targeted anticancer therapies largely depends on the correct understanding of the dormant state of cancer cells, since it is increasingly regarded to fuel tumor recurrence. The concept of cancer cell dormancy is often considered as an adaptive response of cancer cells to stress, and, therefore, is limited. It is possible that the cancer dormant state is not a privilege of cancer cells but the same reproductive survival strategy as diapause used by embryonic stem cells (ESCs).

The upregulation of Ulk1-dependent autophagy does not require the p53 activity in mouse embryonic stem cells.

Autophagy is known to play a critical role in the early stages of embryogenesis including the formation of blastocyst. The existence of p53 protein-deficient mice may identify that p53 is not indispensable for the activation of autophagy in pluripotent cells derived from the inner cell mass of the blastocyst. We utilized a p53-knockout (KO) mouse embryonic stem cell (mESC) line to investigate the contribution of p53 in autophagy.

Inducible Ulk1 expression activates the p53 protein in mouse embryonic stem cells.

Defective pluripotent cells are removed from embryos prior to differentiation, presumably due to upregulation of the p53 pathway. However, the mechanism underlying p53 protein activation is still unknown. Embryonic stem cells (ESCs), corresponding to cells of the preimplantation blastocyst, likely have similar mechanisms for abnormal cell elimination.

Resveratrol-induced p53 activation is associated with autophagy in mouse embryonic stem cells.

Resveratrol is a natural polyphenol with several therapeutic effects, in particular, inducing p53-dependent cell cycle arrest and/or apoptosis in tumor cells. Resveratrol-induced p53 activation may trigger differentiation and apoptosis in embryonic stem cells (ESCs). We show that resveratrol activates p53 that is negatively regulated by SIRT1 deacetylation on Lys379 and positively by AMPK phosphorylation on Ser15 in mouse ESCs (mESCs).

Associations of Del 301-303 alpha2B-adrenoceptor gene polymorphism with central hemodynamic parameters in the northern Russian population.

The ADRA2B gene 301-303 I/D polymorphism is associated with various cardiovascular phenotypes. However, an association of genotypes with the timing structure of cardiac cycle remains unclear. The central hemodynamic parameters were assessed by pulse wave analysis in 63 residents of the Kola Peninsula (68 N) aged 27-65 yr.

G1 checkpoint is compromised in mouse ESCs due to functional uncoupling of p53-p21Waf1 signaling.

Mouse embryonic stem cells (mESCs) lack of G1 checkpoint despite that irradiation (IR) activates ATM/ATR-mediated DDR signaling pathway. The IR-induced p53 localizes in the nuclei and up-regulates p21/Waf1 transcription but that does not lead to accumulation of p21/Waf1 protein. The negative control of the p21Waf1 expression appears to occur at 2 levels of regulation.

New insights into cell cycle regulation and DNA damage response in embryonic stem cells.

Embryonic stem cells (ESCs) have unlimited proliferative potential, while retaining the ability to differentiate into descendants of all three embryonic layers. High proliferation rate of ESCs is accompanied by a shortening of the G(1) phase and the lack of G(1) checkpoint following DNA damage. The absence of G(1) arrest in ESCs after DNA damage is likely caused by a dysfunction of the p53-dependent p21Waf1 pathway that is a key event for the maintenance of pluripotency.

Combined CYP1A1/GSTM1 at-risk genotypes are overrepresented in squamous cell lung carcinoma patients but underrepresented in elderly tumor-free subjects.

Purpose: Polycyclic aromatic hydrocarbons are activated by cytochrome P450 1A1 (CYP1A1) and inactivated by glutathione S-transferase mu (GSTM1). Therefore, it is expected that a combination of proficient CYP1A1 genotype with deficient GSTM1 variant would result in particularly elevated lung cancer (LC) risk, especially for squamous cell carcinoma (SCC). This study was aimed to validate whether the CYP1A1-C (3801) (CYP1A1*2) allele has an unfavorable significance alone and/or in combination with the GSTM1 deficiency.