An essential saccharide binding domain for the mAb 2C7 established for Neisseria gonorrhoeae LOS by ES-MS and MSn

A study of bacterial surface oligosaccharides were investigated among different strains of Neisseria gonorrhoeae to correlate structural features essential for binding to the MAb 2C7. This epitope is widely expressed and conserved in gonococcal isolates, characteristics essential to an effective candidate vaccine antigen. Sample lipooligosaccharides (LOS), was prepared by a modification of the hot phenol-water method from which de-O-acetylated LOS and oligosaccharide (OS) components were analyzed by ES-MS-CID-MS and ES-MSnin a triple quadrupole and an ion trap mass spectrometer, respectively. Previously documented natural heterogeneity was apparent from both LOS and OS preparations which was admixed with fragments induced by hydrazine and mild acid treatment. Natural heterogeneity was limited to phosphorylation and antenni extensions to the alpha-chain. Mild acid hydrolysis to release OS also hydrolyzed the beta(1-->6) glycosidic linkage of lipid A. OS structures were determined by collisional and resonance excitation combined with MS and multistep MSn which provided sequence information from both neutral loss, and nonreducing terminal fragments. A comparison of OS structures, with earlier knowledge of MAb binding, enzyme treatment, and partial acid hydrolysis indicates a generic overlapping domain for 2C7 binding. Reoccurring structural features include a Hepalpha(1-->3)Hepbeta(1-->5)KDO trisaccharide core branched on the nonreducing terminus (Hep-2) with an alpha(1-->2) linked GlcNAc (gamma-chain), and an alpha-linked lactose (beta-chain) residue. From the central heptose (Hep-1), a beta(1-->4) linked lactose (alpha-chain), moiety is required although extensions to this residue appear unnecessary.      

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.     

Prevention of Aging. Communication I. Individual Enzymatic Variations of the Antioxidant System and a Way to Correct this System by Means of Electrochemically Activated Systems

The effect of electrochemically activated systems (ECAS) on the enzyme activity of the antioxidant system (catalase, peroxidase, and superoxide dismutase) appears to be a normalizing effect that increases supressed enzyme activity and decreases enhanced enzyme activity. Baseline enzyme activity is characterized by significant individual variations in both animals and humans. The effect of ECAS may be explained by the training effect of electroactivated systems due to the excess of electrons, with the ECAS redox potential being negative.     

Diagnosis of Aging. Report II. Age Dynamics of Correlation between the Biological Markers of Aging

The correlation analysis of the relationship between the biological age markers in three age groups revealed alterations in the number and rate of correlations up to the inversion of these relations in some cases. As a whole, the observed changes can be characterized as a rearrangement at the regulatory interactions with an increase at the strain of the functioning of the body organs and systems at the middle age and an alteration in the coordination of the body system functioning at the elderly age. The ways of the optimization of the standard methods for the biological age measurement are discussed with regard to these changes.