Appetizing rancidity of apoptotic cells for macrophages: oxidation,externalization, and recognition of phosphatidylserine

Programmed cell death (apoptosis) functions as a mechanism to eliminate unwanted or irreparably damaged cells ultimately leading to their orderly phagocytosis in the absence of calamitous inflammatory responses. Recent studies have demonstrated that the generation of free radical intermediates and subsequent oxidative stress are implicated as part of the apoptotic execution process. Oxidative stress may simply be an unavoidable yet trivial byproduct of the apoptotic machinery; alternatively, intermediates or products of oxidative stress may act as essential signals for the execution of the apoptotic program. This review is focused on the specific role of oxidative stress in apoptotic signaling, which is realized via phosphatidylserine-dependent pathways leading to recognition of apoptotic cells and their effective clearance. In particular, the mechanisms involved in selective phosphatidylserine oxidation in the plasma membrane during apoptosis and its association with disturbances of phospholipid asymmetry leading to phosphatidylserine externalization and recognition by macrophage receptors are at the center of our discussion. The putative importance of this oxidative phosphatidylserine signaling in lung physiology and disease are also discussed.     

Low-Molecular-Weight Compounds

Self-association of caffeine has been investigated using mass spectrometry. It was found that associates are composed of caffeine trimers and hexamers. The possibility of complex formation of caffeine with triterpene glycosides 3-O-α-L-rhamnopyranosyl-(1→2)-O-α-L-arabinopyranoside of hederagenin and its 28-O-α-L-rhamnopyranosyl-(1→4)-O-β-D-glucopyranosil-(1→6)-O-β-D-glucopyranosil ester have been considered. Under the experimental conditions, inclusion compounds do not form and only self-associates of caffeine and glycosides are found.     

Biological significance of the Gornoslinkinskaya Riverbed Depression in the Irtysh

Distribution of fish in the Gornoslinkinskaya Riverbed Depression in the Irtysh is considered in relation to the time of day and to the season. Fish aggregations are characterized quantitatively and by their size and species composition. The major part of the fish population of the depression consists of fish juveniles. The biological significance of the riverbed depression is polyfunctional. The universal traits of the ecosystems of large river basins and mechanisms of their occupation by fish are discussed.     

Anthrax toxin receptor 2 functions in ECM homeostasis of the murine reproductive tract and promotes MMP activity

Anthrax Toxin Receptor proteins function as receptors for anthrax toxin, however physiological activity remains unclear. To evaluate the biological role of Antxr2, we generated Antxr2-/- mice. Antxr2-/- mice were viable, however Antxr2 is required for parturition in young females and for preserving fertility in older female mice. Histological analysis of the uterus and cervix revealed aberrant deposition of extracellular matrix proteins such as type I collagen, type VI collagen and fibronectin. A marked disruption of both the circular and longitudinal myometrial cell layers was evident in Antxr2-/- mice. These changes progressed as the mice aged, resulting in a thickened, collagen dense, acellular stroma and the disappearance of normal uterine architecture. To investigate the molecular mechanism underlying the uterine fibrosis we performed immunoblotting for MMP2 using uterine lysates and zymography using conditioned medium from Antxr2-/- mouse embryonic fibroblasts and found reduced levels of activated MMP2 in both. This prompted us to investigate MT1-MMP status, as MMP2 processing is regulated by MT1-MMP. We found MT1-MMP activity, as measured by MMP2 processing and activation, was enhanced by expression of either ANTXR1 or ANTXR2. We identified an ANTXR2/MT1-MMP complex and demonstrated that MT1-MMP activity is dependent on ANTXR2 expression levels in cells. Thus, we have discovered that ANTXR1 and ANTXR2 function as positive regulators of MT1-MMP activity.     

Mass spectrometric study on plant glycosides molecular complexation with streptocid (sulfanylamide)

Molecular complexation of streptocid (sulfanylamide) with 3-O-??-L-rhamnopyranosyl-(1 ?? 2)-O-??-L-arabinopyranoside of hederagenin (??-hederin) and its 28-O-??-L-rhamnopyranosyl -(1 ?? 4)-O-??-D-glucopyranosyl-(1 ?? 6)-O-??-D-glucopyranosyl ester (hedera saponin C) has been studied with electrospray ionization mass spectrometry for the first time. It was established that ??-hederin forms a 1: 1 complex with streptocid. Hedera saponin C complexes with streptocid with the molar ratio 1: 1, 2: 1, and 2: 2 were more stable. Conclusions were drawn about the influence of the glycosides and streptocid structure on complexation.     

L1 (LINE-1) retrotransposable elements provide a "fossil" record of the phylogenetic history of murid rodents

The single most difficult problem in phylogenetic analysis is deciding whether a shared taxonomic character is due to common ancestry or one that appeared independently due to convergence, parallelism, or reversion to an ancestral state. Mammalian L1 retrotransposons undergo periodic amplifications in which multiple copies of the elements are interspersed in the genome. Because these elements apparently are transmitted only by inheritance and are retained in the genome, a shared L1 amplification event can only be an inherited ancestral character. We propose that L1 amplification events can be an excellent tool for analyzing mammalian evolution and demonstrate here how we addressed several refractory problems in rodent systematics using L1 DNA as a taxonomic character.      

Immunoenzyme analysis of ovarian metastatic antigen-8]

Immunoenzymatic method for the determination of new ovarian-metastatic antigen-8 in human blood serum was worked out. OMA-8 level was studied in blood serum of 40 healthy women, 40 healthy men, 16 neonates, 33 pregnant women, 103 patients with genital tumours. It was found out that OMA-8 level in blood serum of healthy women changed between 2 to 15.4 micrograms/l, in men between 5-17.0 microgramS/l. OMA-8 concentration higher than 15.4 micrograms/ was considered elevated. The elevated OMA-8 level was marked in neonates (100%) and in pregnant (39.3%). High level was discovered in the amniotic fluid.     

Winter Fish Distribution in the Riverbed Depression in the Urtysh River

Journal of Ichthyology - Winter fish distribution is investigated by means of computerized hydroacoustic complexes in the largest riverbed depression in the Irtysh. Fish aggregations whose...     

Fluorescent gramicidin derivatives for single-molecule fluorescence and ion channel measurements.

Single-molecule spectroscopies in combination with single-channel patch-clamp measurements have the potential for providing new information on ion channel gating processes. Fluorescent gramicidin derivatives could provide a means for calibrating such experiments since the structure of the open channel is known and the mechanism of gating (peptide dimerization) is generally agreed. We describe here the synthesis and characterization of two pairs of gramicidin derivatives that should prove useful for such studies. They contain robust fluorophores, undergo resonance energy transfer (FRET) when they dimerize, and have single-channel properties close to those of the wild-type channel.     

A mass spectrometry study of the self-association of glycyrrhetinic acid molecules

The formation of self-associates of glycyrrhetinic acid (GLA), an aglycone of glycyrrhizic acid (GA), has been studied by electrospray ionization mass spectrometry. It has been shown for the first time that, analogously to triterpene saponins having free carboxyl groups, GLA stereoisomers can form self-associates. The capacity of GLA to form self-associates has been confirmed by the mass spectrometry data. It has been found that the ionization of GLA self-associates with the formation of an anion proceeds rather weakly. The ionization of GLA in the positive ion mode goes on effectively and makes it possible to record multidimensional structures of one to eight 18α-GLA molecules and from one to nine 18β-GLA molecules. The structure of GLA associates and their stability are demonstrated most comprehensively in positive ion mass spectra. As a whole, the sets and intensity of peaks for 18α- and 18β-GLA correlate well. The results of the mass spectrometry study show the capacity of 18α- and 18β-GLA stereoisomers to form self-associates, which indicates a high potentiality of GLA in providing noncovalent interactions during the formation of supramolecular complexes. Similarly to the saponins of licorice and ivy, GLA stereoisomers may form a potential basis for the synthesis of a new generation of noncovalent molecular complexes and novel highly effective medicinal substances owing to a possible improvement in bioaccessibility and possible synergistic effects.