Transgenerational and intergenerational effects of early childhood famine exposure in the cohort of offspring of Leningrad Siege survivors.

Famine exposure during early life development can affect disease risk in late-life period, yet, transmission of phenotypic features from famine-exposed individuals to the next generations has not been well characterized. The purpose of our case-control study was to investigate the association of parental starvation in the perinatal period and the period of early childhood with the phenotypic features observed in two generations of descendants of Leningrad siege survivors. We examined 54 children and 30 grandchildren of 58 besieged Leningrad residents who suffered from starvation in early childhood and prenatal age during the Second World War. Controls from the population-based national epidemiological ESSE-RF study (n = 175) were matched on sex, age and body mass index (BMI). Phenotypes of controls and descendants (both generations, children and grandchildren separately) were compared, taking into account multiple testing. Comparison of two generations descendants with corresponding control groups revealed significantly higher creatinine and lower glomerular filtration rate (GFR), both in meta-analysis and in independent analyses. The mean values of GFR for all groups were within the normal range (GFR less than 60 mL/min/1.73 m2 was recorded in 2 controls and no one in DLSS). Additionally, independent of the creatinine level, differences in the eating pattern were detected: insufficient fish and excessive red meat consumption were significantly more frequent in the children of the Leningrad siege survivors compared with controls. Blood pressure, blood lipids and glucose did not differ between the groups. Parental famine exposure in early childhood may contribute to a decrease in kidney filtration capacity and altered eating pattern in the offspring of famine-exposed individuals.

Case Report: Supernormal Vascular Aging in Leningrad Siege Survivors.

Age-related changes in the vascular system play an important role in the biological age and lifespan of a person and maybe affected from an early age onward. One of the indicators of changes in the vascular system is arterial wall stiffness and its main measure, i.e., carotid-femoral pulse wave velocity (cfPWV). We examined arterial wall stiffness in a sample of 305 Leningrad Siege survivors to assess how hunger and stressful conditions during fetal development and early childhood affected the state of the cardiovascular system at a later age and what factors may neutralize the negative impact sustained in early childhood. Here, we presented an evaluation of two unique patients with supernormal vascular aging (SUPERNOVA) phenotype from this cohort and described the details of congruence between hereditary resistance and practiced lifestyle yielding slower biological aging rate.

FTIR Spectroscopy Study of the Secondary Structure Changes in Human Serum Albumin and Trypsin under Neutral Salts.

The effect of neutral salts on protein conformation was first analyzed by Hofmeister in 1888, however, even today this phenomenon is not completely understood. To clarify this effect, we studied changes in the secondary structure of two proteins: human serum albumin with predominantly α-helical structure and porcine pancreas ß-trypsin with the typical ß-structural arrangement in aqueous solutions of neutral salts (KSCN, KCl, (NH4)2SO4). The changes in the secondary structure were studied at 23 °C and 80 °C by using the second derivative deconvolution method of the IR spectra. Our results demonstrated that the ability of the salts to stabilize/destabilize these two proteins correlates with the Hofmeister series of ions. At the same time, some exceptions were also observed. The destabilization of the native structures of both α-helical albumin and ß-structural trypsin upon interaction with neutral salts leads to the formation of intermolecular ß-sheets typical for amyloid fibrils or amorphous aggregates. Thus, our quantitative FTIR-spectroscopy analysis allowed us to further clarify the mechanisms and complexity of the neutral salt actions on protein structures which may lead to strategies preventing unwelcome misfolding of proteins.

Census of halide-binding sites in protein structures.

MOTIVATION: Halides are negatively charged ions of halogens, forming fluorides (F-), chlorides (Cl-), bromides (Br-) and iodides (I-). These anions are quite reactive and interact both specifically and non-specifically with proteins. Despite their ubiquitous presence and important roles in protein function, little is known about the preferences of halides binding to proteins. To address this problem, we performed the analysis of halide-protein interactions, based on the entries in the Protein Data Bank. RESULTS: We have compiled a pipeline for the quick analysis of halide-binding sites in proteins using the available software. Our analysis revealed that all of halides are strongly attracted by the guanidinium moiety of arginine side chains, however, there are also certain preferences among halides for other partners. Furthermore, there is a certain preference for coordination numbers in the binding sites, with a correlation between coordination numbers and amino acid composition. This pipeline can be used as a tool for the analysis of specific halide-protein interactions and assist phasing experiments relying on halides as anomalous scatters. AVAILABILITY AND IMPLEMENTATION: All data described in this article can be reproduced via complied pipeline published at https://github.com/rostkick/Halide_sites/blob/master/README.md. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Systematic FTIR Spectroscopy Study of the Secondary Structure Changes in Human Serum Albumin under Various Denaturation Conditions.

Human serum albumin (HSA) is the most abundant protein in blood plasma. HSA is involved in the transport of hormones, fatty acids, and some other compounds, maintenance of blood pH, osmotic pressure, and many other functions. Although this protein is well studied, data about its conformational changes upon different denaturation factors are fragmentary and sometimes contradictory. This is especially true for FTIR spectroscopy data interpretation. Here, the effect of various denaturing agents on the structural state of HSA by using FTIR spectroscopy in the aqueous solutions was systematically studied. Our data suggest that the second derivative deconvolution method provides the most consistent interpretation of the obtained IR spectra. The secondary structure changes of HSA were studied depending on the concentration of the denaturing agent during acid, alkaline, and thermal denaturation. In general, the denaturation of HSA in different conditions is accompanied by a decrease in α-helical conformation and an increase in random coil conformation and the intermolecular ß-strands. Meantime, some variation in the conformational changes depending on the type of the denaturation agent were also observed. The increase of ß-structural conformation suggests that HSA may form amyloid-like aggregates upon the denaturation.