Design of the blood group AB glycotope

Although the nature of the blood groups A and B has been comprehensively studied for a long time, it is still unclear as to what exactly is the epitope that is recognized by antibodies having AB specificity, i.e. monoclonal and polyclonal antibodies which are capable of interacting equally well with the antigens GalNAcα 1-3(Fucα 1-2)Gal (A trisaccharide) and Galα 1-3(Fucα 1-2)Gal (B trisaccharide), but do not react with their common fragment Fucα 1-2Gal. We have supposed that besides Fucα 1-2Gal, A and B antigens have one more shared epitope. The trisaccharides A and B are practically identical from the conformational point of view, the only difference being situated at position 2 of Galα residue, i.e. trisaccharide A has a NHAc group, whereas trisaccharide B has a hydroxyl group (see formulas). We have hypothesized that the AB-epitope should be situated in the part of the molecule that is opposite to the NHAc group of GalNAc residue. In order to test this hypothesis we have synthesized a polymeric conjugate in such a way that de-N-acetylated A-trisaccharide is attached to a polymer via the nitrogen in position C-2 of the galactosamine residue. In this conjugate the supposed AB-epitope should be maximally accessible for antibodies from the solution, whereas the discrimination site of antigens A and B by the antibodies should be maximally hidden due to the close proximity of the polymer. Interaction with several anti-AB monoclonal antibodies revealed that a part of them really interacted with the synthetic AB-glycotope, thus confirming our hypothesis. Moreover, similar antibodies were revealed in the blood of healthy blood group 0 donors. Analysis of spatial models was performed in addition to identify the hydroxyl groups of Fuc, Galα, and Galβ residues, which are particularly involved in the composition of the AB-glycotope. Published in 2005.     

Correlations of life-span variation parameters in 128 successive generations of Drosophila melanogaster with changes in atmospheric pressure and geomagnetic activity

Correlations between the parameters of life-span (LS) distribution of Drosophila melanogaster, including mean LS (MLS) and the time of 10 and 90% population mortality, and some geophysical parameters that are usually beyond the control of researchers dealing with laboratory cultures, including atmospheric pressure, solar activity indices (Wolfs sunspot numbers and 2,800-MHz radio flux), and geomagnetic activity (planetary index, K_p), were studied. Geophysical data were obtained from free-access official web sites of the National Oceanic & Atmospheric Administration of the US Department of Commerce and the Institute of Terrestrial Magnetism and Radiowave Propagation of the Russian Academy of Sciences. The geophysical parameters were calculated only for the period corresponding to 10 days of preimaginal development of the flies from egg to imago. Canonical correlation analysis, calculation of the non-parametric Spearman rank-order correlation coefficients, and graphical data analysis were used. Highly significant correlations between parameters of LS distribution in males and females and environmental factors, such as the atmospheric pressure on the 4th and 5th day of development and geomagnetic activity indices (K_p) on the 6th and 10th day of development were found, with correlation coefficients varying from 0.31 to 0.37 (P<0.02). Assuming a causal relationship between geophysical factors and LS, it may be hypothesized that energetically weak environmental factors determine the formation of LS oscillatory dynamics in laboratory populations. The possible mechanisms underlying the contribution of these environmental factors to the LS variation in successive generations are discussed.     

Model of radiation-accelerated aging and its specific features

We conducted a lifetime study of the content of oxidized and methylated guanine in the urine of intact and irradiated mice. For statistical processing of the results, we used the trial period method created by A.A. Konradov, which was unpublished during the author’s lifetime. We prove that there are oscillating components in the age dependence of the concentration of oxidized and methylated guanine in mice urine. For intact animals, a 7-month oscillation period is the most probable (p = 0.001). For irradiated mice, a disruption in the seasonal oscillation rhythm in the concentration of oxidized and methylated guanine in urine was noted, which is peculiar to radiation-accelerated aging.     

Analysis of Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 Gene K121Q Polymorphism Association with Some Risk Factors of Atherosclerosis in Patients with Acute Coronary Syndrome

The present study was performed to investigate whether common single-nucleotide polymorphism K121Q (rs1044498) of the ENPP1 gene is associated with the known risk factors of atherosclerosis (overweight, dyslipoproteinemia, hypertension, diabetes, smoking, and hypercoagulability) in persons with acute coronary syndrome. Venous blood of 118 patients was genotyped for the polymorphism by PCR and restriction fragment length polymorphism method. In patients divided into two subgroups according to their genotype (KK and KQ + QQ), the statistically significant differences were revealed only for plasma LDL-cholesterol level and fibrinolytic activity. The carriers of minor allele (KQ + QQ) had lower LDL-cholesterol concentration and the time of fibrinolysis than the major allele homozygotes (KK). The division of patients into subgroups according to presence or absence of some risk factors for atherosclerosis showed no statistically significant differences between K121Q genotype distributions for any of the comparison.     

Dynamics of potentially pathogenic microflora of the water and pike perch in the Volga Delta

On the basis of long-term (1995–2010 and 2013–2014) microbiological monitoring of water and pike perch in the various water areas of the Volga Delta, four dominant groups of bacteria from the family Enterobacteriaceae and genera Aeromonas, Flavobacterium, and Pseudomonas were identified. The results of studies on the species composition of water microflora and fish from natural populations and artificial breeding are summarized. The prevalence of potentially pathogenic microflora in the water and fish over the indicative ones has been shown. Water temperature influences the seasonal cycles of microorganisms and their pathogenicity factors, which determine their fast adaptation to living in different ecological niches.     

A randomised, blinded, placebo-controlled trial in dementia patients continuing or stopping neuroleptics (the DART-AD trial)

Background

There have been increasing concerns regarding the safety and efficacy of neuroleptics in people with dementia, but there are very few long-term trials to inform clinical practice. The aim of this study was to determine the impact of long-term treatment with neuroleptic agents upon global cognitive decline and neuropsychiatric symptoms in patients with Alzheimer disease.

Methods and Findings

Design: Randomised, blinded, placebo-controlled parallel two-group treatment discontinuation trial.Setting: Oxfordshire, Newcastle and Gateshead, London and Edinburgh, United Kingdom.Participants: Patients currently prescribed the neuroleptics thioridazine, chlorpromazine, haloperidol trifluoperazine or risperidone for behavioural or psychiatric disturbance in dementia for at least 3 mo.Interventions: Continue neuroleptic treatment for 12 mo or switch to an identical placebo.Outcome measures: Primary outcome was total Severe Impairment Battery (SIB) score. Neuropsychiatric symptoms were evaluated with the Neuropsychiatric Inventory (NPI).Results: 165 patients were randomised (83 to continue treatment and 82 to placebo, i.e., discontinue treatment), of whom 128 (78%) commenced treatment (64 continue/64 placebo). Of those, 26 were lost to follow-up (13 per arm), resulting in 51 patients per arm analysed for the primary outcome. There was no significant difference between the continue treatment and placebo groups in the estimated mean change in SIB scores between baseline and 6 mo; estimated mean difference in deterioration (favouring placebo) −0.4 (95% confidence interval [CI] −6.4 to 5.5), adjusted for baseline value (p = 0.9). For neuropsychiatric symptoms, there was no significant difference between the continue treatment and placebo groups (n = 56 and 53, respectively) in the estimated mean change in NPI scores between baseline and 6 mo; estimated mean difference in deterioration (favouring continue treatment) −2.4 (95% CI −8.2 to 3.5), adjusted for baseline value (p = 0.4). Both results became more pronounced at 12 mo. There was some evidence to suggest that those patients with initial NPI ≥ 15 benefited on neuropsychiatric symptoms from continuing treatment.

Conclusions

For most patients with AD, withdrawal of neuroleptics had no overall detrimental effect on functional and cognitive status. Neuroleptics may have some value in the maintenance treatment of more severe neuropsychiatric symptoms, but this benefit must be weighed against the side effects of therapy.Trial registration: Cochrane Central Registry of Controlled Trials/National Research Register (#ISRCTN33368770).