Direct effects of interleukin-7 on the function of human T cells <Emphasis Type="Italic">in vitro</Emphasis>

CD3+ T lymphocytes were isolated by positive magnetic separation from the peripheral blood of healthy donors. In the absence of any additional activating stimuli, interleukin-7 (IL-7) was shown to augment the levels of T cells expressing CD25 activation marker both in CD4-positive and in CD4-negative effector memory (CD45RA^-CD197^-) T cell subsets, as well as in terminally differentiated (CD45RA⁺CD197^-) T cells, without significantly affecting the activation status of naive (CD45RA⁺CD197⁺) and central memory (CD45RA^-CD197⁺) T cells. In addition, IL-7 noticeably enhanced the production of IL-2, interferon-γ (IFN-γ), and IL-10, but not IL-4, in T cells. The direct effects of IL-7 on T cell activation induced in vitro by MACSiBead? particles coated with CD2, CD3, and CD28 antibodies (Abs) were also investigated. Upon cell activation, IL-7 significantly augmented the levels of CD25+ T cells in naive (CD45RA+CD197+), central memory (CD45RA^-CD197⁺), and effector memory (CD45RA^-CD197^-) T-cell compartments. In addition, IL-7 facilitated activation of CD4^- (but not CD4⁺) terminally differentiated effector (CD45RA⁺CD197^-) T cells. Finally, IL-7 was found to upregulate the production of IL-2, IFN-γ, IL-4, and IL-10 by activated T cells. In conclusion, we speculate that IL-7 is capable of enhancing functional T cell activity without causing significant functional inbalance between various T cell subsets.     

Photoconsumption of molecular oxygen on both donor and acceptor sides of photosystem II in Mn-depleted subchloroplast membrane fragments

Oxygen consumption in Mn-depleted photosystem II (PSII) preparations under continuous and pulsed illumination is investigated. It is shown that removal of manganese from the water-oxidizing complex (WOC) by high pH treatment leads to a 6-fold increase in the rate of O₂ photoconsumption. The use of exogenous electron acceptors and donors to PSII shows that in Mn-depleted PSII preparations along with the well-known effect of O₂ photoreduction on the acceptor side of PSII, there is light-induced O₂ consumption on the donor side of PSII (nearly 30% and 70%, respectively). It is suggested that the light-induced O₂ uptake on the donor side of PSII is related to interaction of O₂ with radicals produced by photooxidation of organic molecules. The study of flash-induced O₂ uptake finds that removal of Mn from the WOC leads to O₂ photoconsumption with maximum in the first flash, and its yield is comparable with the yield of O₂ evolution on the third flash measured in the PSII samples before Mn removal. The flash-induced O₂ uptake is drastically (by a factor of 1.8) activated by catalytic concentration (5-10 μM, corresponding to 2-4 Mn per RC) of Mn²⁺, while at higher concentrations (> 100 μM) Mn²⁺ inhibits the O₂ photoconsumption (like other electron donors: ferrocyanide and diphenylcarbazide). Inhibitory pre-illumination of the Mn-depleted PSII preparations (resulting in the loss of electron donation from Mn²⁺) leads to both suppression of flash-induced O₂ uptake and disappearance of the Mn-induced activation of the O₂ photoconsumption. We assume that the light-induced O₂ uptake in Mn-depleted PSII preparations may reflect not only the negative processes leading to photoinhibition but also possible participation of O₂ or its reactive forms in the formation of the inorganic core of the WOC.     

Utility Rate Equations of Group Population Dynamics in Biological and Social Systems

We present a novel system of equations to describe the evolution of self-organized structured societies (biological or human) composed of several trait groups. The suggested approach is based on the combination of ideas employed in the theory of biological populations, system theory, and utility theory. The evolution equations are defined as utility rate equations, whose parameters are characterized by the utility of each group with respect to the society as a whole and by the mutual utilities of groups with respect to each other. We analyze in detail the cases of two groups (cooperators and defectors) and of three groups (cooperators, defectors, and regulators) and find that, in a self-organized society, neither defectors nor regulators can overpass the maximal fractions of about each. This is in agreement with the data for bee and ant colonies. The classification of societies by their distance from equilibrium is proposed. We apply the formalism to rank the countries according to the introduced metric quantifying their relative stability, which depends on the cost of defectors and regulators as well as their respective population fractions. We find a remarkable concordance with more standard economic ranking based, for instance, on GDP per capita.     

Ancient pathogen DNA in human teeth and petrous bones

Recent ancient DNA (aDNA) studies of human pathogens have provided invaluable insights into their evolutionary history and prevalence in space and time. Most of these studies were based on DNA extracted from teeth or postcranial bones. In contrast, no pathogen DNA has been reported from the petrous bone which has become the most desired skeletal element in ancient DNA research due to its high endogenous DNA content. To compare the potential for pathogenic aDNA retrieval from teeth and petrous bones, we sampled these elements from five ancient skeletons, previously shown to be carrying Yersinia pestis. Based on shotgun sequencing data, four of these five plague victims showed clearly detectable levels of Y. pestis DNA in the teeth, whereas all the petrous bones failed to produce Y. pestis DNA above baseline levels. A broader comparative metagenomic analysis of teeth and petrous bones from 10 historical skeletons corroborated these results, showing a much higher microbial diversity in teeth than petrous bones, including pathogenic and oral microbial taxa. Our results imply that although petrous bones are highly valuable for ancient genomic analyses as an excellent source of endogenous DNA, the metagenomic potential of these dense skeletal elements is highly limited. This trade‐off must be considered when designing the sampling strategy for an aDNA project.     

Modelling of the prebiotic synthesis of oligopeptides: silicate catalysts help to overcome the critical stage

On the basis of experimental studies of the initial stages of glycine oligomerization in aqueous suspension of zeolite and kaolinite catalysts, a model is suggested for the prebiotic synthesis of oligopeptides from -amino acids. The formation of linear dipeptides by hydrolysis of one amide bond in the cyclic piperazinedione intermediate (formed from glycine spontaneously) is found to be the critical stage of the reaction. This stage is base catalyzed and its rate increases when pH of the medium goes up. The linear glycyl-glycine yield rises under effect of hydroxyl anions generated from different sources including insoluble silicates and soluble sodium bicarbonate. During prebiotic evolution silicates capable of cation-exchange can serve as local sources of the hydroxyl anions which dramatically accelerate formation of linear dipeptides from cyclic ones. Oligopeptides of higher molecular weight are then easily formed from the linear dipeptides at neutral pH, even in the absence of catalysts or sources of energy (e.g. such as light). The described catalytic synthesis could occur in the proximity of submarine hydrothermal vents.     

Developing criteria for evaluation of geroprotectors as a key stage toward translation to the clinic

In the coming decades, a massive shift in the aging segment of the population will have major social and economic consequences around the world. One way to offset this increase is to expedite the development of geroprotectors, substances that slow aging, repair age‐associated damage and extend healthy lifespan, or healthspan. While over 200 geroprotectors are now reported in model organisms and some are in human use for specific disease indications, the path toward determining whether they affect aging in humans remains obscure. Translation to the clinic is hampered by multiple issues including absence of a common set of criteria to define, select, and classify these substances, given the complexity of the aging process and their enormous diversity in mechanism of action. Translational research efforts would benefit from the formation of a scientific consensus on the following: the definition of ‘geroprotector’, the selection criteria for geroprotectors, a comprehensive classification system, and an analytical model. Here, we review current approaches to selection and put forth our own suggested selection criteria. Standardizing selection of geroprotectors will streamline discovery and analysis of new candidates, saving time and cost involved in translation to clinic.     

Quantification of the Blood Platelet Reactivity in the ADP-Induced Model of Non-Lethal Pulmonary Thromboembolism in Mice with the Use of Laser Doppler Flowmetry

IntroductionThe paper describes an alternative method for quantification of in vivo ADP-induced thromboembolism. The aim of the studies was to develop a method of quantification which would not require either extravasation or labelling of platelets. Our proposed approach is based on the monitoring of changes of blood flow with the use of laser Doppler flowmetry.ResultsThe injection of ADP resulted in a dose-dependent reduction of the blood flow in the mesentery. These responses were fully attributable to blood platelet aggregation, as shown by the lack of the effect in platelet-depleted mice, and significantly reduced responses in mice pretreated with cangrelor and eptifibatide. No platelet aggregate formation in mesenteric vessels was revealed by intravital microscopy, while ex vivo imaging showed accumulation of fluorescent labelled platelets in the lung.ConclusionsInjection of ADP to the venous system results in the formation of platelet aggregates predominantly in the lung. This results in reversible blood flow cessation in peripheral blood vessels. The measurement of this blood flow cessation in the mesentery allows indirect measurement of ADP-induced pulmonary thromboembolism. We suggest that this approach can be useful for in vivo screening for antiplatelet drug candidates.     

Perylenoyl- and anthrylvinyl-labeled lipids as membrane probes

The properties of a new family of lipid-specific fluorescent probes, a fatty acid, a phosphatidylcholine and a sphingomyelin, bearing a 3-perylenoyl-labeled hydrophobic chain, are described. Perylenoyl-labeled lipids readily enter the lipid bilayer, the fluorophore being localized in the apolar region of the membrane. The perylenoyl fluorophore is characterized by a high quantum yield, its fluorescence parameters (λ_ex 446 nm, λ_em 479–545 nm) permit to apply it as an acceptor of excitation energy from the 9-anthrylvinyl fluorophore used earlier for phospholipid labeling (Molotkovsky, Jul. G.; Manevich, Y.M., Gerasimova, E.N., Molotkovskaya, I.M., Polessky, V.A. and Bergelson, L.D. (1982) Eur. J. Biochem. 122, 573–579). The anthrylvinyl-labeled lipids were shown to be capable to report phase segregation between the corresponding prototype lipids in model systems. The combined use of anthrylvinyl- and perylenoyl-labeled lipids opens additional possibilities for investigation of lipid-lipid and lipid-protein interactions in artificial and biological membranes. Perylenoyl-labeled lipids appeared also to be useful as fluorescent dyes in cytological studies.