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An electromagnetic wave (EMW) interacting with the moving singularity of the charged particle flux undergoes the reflection and absorption as well as frequency change due to Doppler effect and nonlinearity. The singularity corresponding to a caustic in plasma flow with inhomogeneous velocity can arise during the breaking of the finite amplitude Langmuir waves due to nonlinear effects. A systematic analysis of the wave-breaking regimes and caustics formation is presented and the EMW reflection coefficients are calculated.

Identification of molecular targets and mechanism of action is always a challenge, in particular – for natural compounds due to inherent chemical complexity. BP-Cx-1 is a water-soluble modification of hydrolyzed lignin used as the platform for a portfolio of innovative pharmacological products aimed for therapy and supportive care of oncological patients. The present study describes a new approach, which combines in vitro screening of potential molecular targets for BP-Cx-1 using Diversity Profile - P9 panel by Eurofins Cerep (France) with a search of possible active components in silico in ChEMBL - manually curated chemical database of bioactive molecules with drug-like properties. The results of diversity assay demonstrate that BP-Cx-1 has multiple biological effects on neurotransmitters receptors, ligand-gated ion channels and transporters. Of particular importance is that the major part of identified molecular targets are involved in modulation of inflammation and immune response and might be related to tumorigenesis. Characterization of molecular composition of BP-Cx-1 with Fourier Transform Ion Cyclotron Resonance Mass Spectrometry and subsequent identification of possible active components by searching for molecular matches in silico in ChEMBL indicated polyphenolic components, nominally, flavonoids, sapogenins, phenanthrenes, as the major carriers of biological activity of BP-Cx-1. In vitro and in silico target screening yielded overlapping lists of proteins: adenosine receptors, dopamine receptor DRD4, glucocorticoid receptor, serotonin receptor 5-HT1, prostaglandin receptors, muscarinic cholinergic receptor, GABAA receptor. The pleiotropic molecular activities of polyphenolic components are beneficial in treatment of multifactorial disorders such as diseases associated with chronic inflammation and cancer.

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The perinatal (prenatal and early neonatal) period is a critical stage for hypothalamic programming of sexual differentiation as well as for the development of energy and metabolic homeostasis. We hypothesized that neonatal treatment with antidiabetic drug biguanide metformin would positively modify regulation of growth hormone -IGF-1 -insulin signaling pathway slowing down aging and improving cancer preventive patterns in rodents. To test this hypothesis male and female 129/Sv mice were s.c. injected with metformin (100 mg/kg) at the 3rd, 5th and 7th days after birth. Metformin-treated males consumed less food and water and their body weight was decreased as compared with control mice practically over their entire lifespan. There were no significant differences in age-related dynamics of food and water consumption in females and they were heavier than controls. The fraction of mice with regular estrous cycles decreased with age and demonstrated a tendency to decrease in the females neonatally treated with metformin. Neonatal exposure to metformin practically failed to change the extent of hormonal and metabolic parameters in blood serum of male and female mice. In males, neonatal metformin treatment significantly increased the mean life span (C20%, P < 0.05) and slightly increased the maximum life span (C3.5%). In females, the mean life span and median in metformin-treated groups were slightly decreased (¡9.1% and ¡13.8% respectively, P > 0.05) in comparison to controls, whereas mean life span of last 10% survivors and maximum life span were the same as in controls. Almost half (45%) of control male mice and 71.8% male mice neonatally exposed to metformin survived up to 800 d of age, the same age was achieved by 54.3% of mice in control female group and 30% of metformin-treated females (P < 0.03). Thus, neonatal metformin exposure slows down aging and prolongs lifespan in male but not in female mice.

Combined pretreatment by hyperoxia and dexamethasone improved postischemic heart function, but did not reduce infarct size compared to single pretreatment groups. Except of a possible role of ERK1/2, protection depended neither on survival kinases nor heat shock protein 72.

Parametric models for survival data help to differentiate aging from other lifespan determinants. However, such inferences suffer from small sizes of experimental animal samples and variable animals handling by different labs. We analyzed control data from a single laboratory where interventions in murine lifespan were studied over decades. The minimal Gompertz model (GM) was found to perform best with most murine strains. However, when several control datasets related to a particular strain are fitted to GM, strikingly rigid interdependencies between GM parameters emerge, consistent with the Strehler-Mildvan correlation (SMC). SMC emerges even when survival patterns do not conform to GM, as with cancer-prone HER2/neu mice, which die at a log-normally distributed age. Numerical experiments show that SMC includes an artifact whose magnitude depends on dataset deviation from conformance to GM irrespectively of the noisiness of small datasets, another contributor to SMC. Still another contributor to SMC is the compensation effect of mortality (CEM): a real tradeoff between the physiological factors responsible for initial vitality and the rate of its decline. To avoid misinterpretations, we advise checking experimental results against a SMC based on historical controls or on subgroups obtained by randomization of control animals. An apparent acceleration of aging associated with a decrease in the initial mortality is invalid if it is not greater than SMC suggests. This approach applied to published data suggests that the effects of calorie restriction and of drugs believed to mimic it are different. SMC and CEM relevance to human survival patterns is discussed.

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