The Locally Optimal Method of Cyclic Alignment to Reveal Latent Periodicities in Genetic Texts: the NAD-binding Protein Sites

A program package has been developed to search for hidden tandem repeats of any specified type in the protein sequence databases. The applied algorithm of the locally optimal cyclic alignment is able to find subsequences possessing a certain profile-based periodicity type when no appreciable homology between periods is observed, as well as in the presence of arbitrary insertions/deletions. The profile can be adjusted to search for the periodicity types structurally and functionally important. The Swiss-Prot database has been analyzed to reveal the periodicities undetectable earlier that are caused by the secondary and super-secondary structure regularities of the NAD-binding sites. In particular, a significant periodicity of 24 aa was found to be characteristic of the absolute majority of domains possessing the Rossman (or Rossman-like) fold and displaying apparent regularity in their secondary structures, not being obvious at the primary structure level.     

Neurobehavioral Dysfunction as a Possible Sentinel of Methylmercury Exposure

The main concern regarding methylmercury neurotoxicity relates to adverse effects on the brain during development. Many environmental chemicals may act as developmental neurotoxicants, but solid documentation from epidemiological studies exists only on methylmercury, lead, and polychlorinated biphenyls (PCBs). Neurobehavioral tests may reveal subtle dysfunctions, but the tests chosen must be valid and appropriate for the setting. In a prospective study in the Faroe Islands, the main neuropsychological functions affected by prenatal methylmercury exposure were attention, language and memory. Deficits in visuospatial function were mainly related to postnatal exposures. These associations were stable after adjustment for confounders and exclusion of the children with the highest exposures to methylmercury and PCBs. Tests with good psychometric properties were more likely to show an association with mercury exposure. Greater sensitivity was also seen with tests administered by specialized academic staff rather than a trained technician. Despite highly significant effects on nervous system function, the deficits were subtle, and mercury exposure explained only a small part of the variation. Available evidence suggests that neurotoxicity may have severe implications on public health, but current methods are not amenable to application as sentinels of adverse health effects in environmental health surveillance.     

Intrauterine growth retarded piglet as a model for humans – Studies on the perinatal development of the gut structure and function

The overall acceptance of pig models for human biomedical studies is steadily growing. Results of rodent studies are usually confirmed in pigs before extrapolating them to humans. This applies particularly to gastrointestinal and metabolism research due to similarities between pig and human physiology. In this context, intrauterine growth retarded (IUGR) pig neonate can be regarded as a good model for the better understanding of the IUGR syndrome in humans. In pigs, the induction of IUGR syndrome may include maternal diet intervention, dexamethasone treatment or temporary reduction of blood supply. However, in pigs, like in humans, circa 8% of neonates develop IUGR syndrome spontaneously. Studies on the pig model have shown changes in gut structure, namely a reduced thickness of mucosa and muscle layers, and delayed kinetic of disappearance of vacuolated enterocytes were found in IUGR individuals in comparison with healthy ones. Functional changes include reduced dynamic of gut mucosa rebuilding, decreased activities of main brush border enzymes, and changes in the expression of proteins important for carbohydrate, amino acids, lipid, mineral and vitamin metabolism. Moreover, profiles of intestinal hormones are different in IUGR and non-IUGR piglets. It is suggested that supplementation of the mothers during the gestation and/or the IUGR offspring after birth can help in restoring the development of the gastrointestinal tract. The pig provides presumably the optimal animal model for humans to study gastrointestinal tract structure and function development in IUGR syndrome.     

The influence of maternal nutrition on expression of genes responsible for adipogenesis and myogenesis in the bovine fetus

The objective of this study was to determine whether altered maternal energy supply during mid-gestation results in differences in muscle histology or genes regulating fetal adipose and muscle development. In total, 22 Angus cross-bred heifers (BW=527.73±8.3 kg) were assigned randomly to the three dietary treatments providing 146% (HIGH; n=7), 87% (INT; n=7) or 72% (LOW; n=8) of the energy requirements for heifers from day 85 to day 180 of gestation. Fetuses were removed via cesarean section at day 180 of gestation and longissimus muscle (LM) and subcutaneous fat were collected and prepared for analysis of gene expression. Samples from the LM and semitendinosus (ST) were evaluated for muscle fiber diameter, area and number. The right hind limb was dissected and analyzed to determine compositional analysis. Fetal growth and muscle histology characteristics of the LM and ST were similar among treatments. Preadipocyte factor-1 expression was up-regulated in fetal LM (P<0.05) of HIGH fetuses as compared with INT, whereas LOW fetuses showed increased CCAAT/enhancer-binding protein-β (C/EBP-β) expression in LM as compared with INT (P<0.05). Peroxisome proliferator-activated receptor γand C/EBP-α did not differ as a result of dietary treatment in LM or subcutaneous fat samples. There was a tendency for increased expression of fatty acid synthase in LM of LOW fetuses as compared with INT (P<0.10). Myogenin was more highly expressed (P<0.05) in LM of the LOW fetuses, whereas μ-calpain expression was increased in the HIGH treatment compared with INT. A tendency for increased expression of IGF-II was observed for both LOW and HIGH fetuses compared with INT (P<0.10). Expression of stearoyl-CoA desaturase, myoblast determination protein 1, myogenic factor 5, myogenic regulatory factor-4, m-calpain, calpastatin, IGF-I and myostatin was similar between treatments. Collectively, these results suggest that fetal growth characteristics are not affected by the level of maternal nutritional manipulation imposed in this study during mid-gestation. However, differences in expression of fetal genes regulating adipose and muscle tissue growth and development could lead to differences in postnatal composition and warrants further investigation.     

Seasonal dispersal of pests: one surge or two?

Many agricultural pest species occur in seasonal metapopulations with a period of asexual reproduction. We use evolutionary theory to predict timing of dispersal for such species, and identify four sequential phases: no dispersal, dispersal from initially occupied patches, dispersal from later colonized patches, and no dispersal. The third type of phase occurs only when reproductive rates are relatively high; we speculate that this could explain why among aphids there can be either one or two waves of dispersal during a season, depending on the species. Our model also explains other features of aphid biology, including a summer crash in colony size, and a decline in the number of colonies towards the end of each reproductive season. The presence of an additional surge of dispersal becomes more likely as season length increases, and does not require further evolution. This could have profound implications for pest management during future climatic warming.     

Genipin normalizes depression-like behavior induced by prenatal stress through inhibiting DNMT1

Synthetic antidepressants in current use for the complex etiopathogeneses of depression have slow response and remission as well as various unpleasant side effects. As a result, it is imperative to develop new antidepressants with more effectiveness and less severe side effects. Recent studies demonstrated that genipin, the aglycon of geniposide, extracted from Gardenia jasminoides Ellis has antidepressive effects. However, knowledge regarding the molecular mechanisms of its antidepressant effects remains limited. Employing a depression-like mouse model, we confirmed that genipin is capable of correcting depressions-like behaviors induced by prenatal stress in offspring from prenatally stressed dams (defined as PRS mice). In further experiments, we found that the effect of genipin on PRS mice occurs through DNA demethylation by inhibiting DNA methyltransferase 1 (DNMT1), normalizing the expression of reduced brain-derived neurotrophic factor (BDNF) in the hippocampus.     

Maternal genome-wide DNA methylation profiling in gestational diabetes shows distinctive disease-associated changes relative to matched healthy pregnancies

Several recent reports have described associations between gestational diabetes (GDM) and changes to the epigenomic landscape where the DNA samples were derived from either cord or placental sources. We employed genome-wide 450K array analysis to determine changes to the epigenome in a unique cohort of maternal blood DNA from 11 pregnant women prior to GDM development relative to matched controls. Hierarchical clustering segregated the samples into 2 distinct clusters comprising GDM and healthy pregnancies. Screening identified 100 CpGs with a mean β-value difference of ≥0.2 between cases and controls. Using stringent criteria, 5 CpGs (within COPS8, PIK3R5, HAAO, CCDC124, and C5orf34 genes) demonstrated potentials to be clinical biomarkers as revealed by differential methylation in 8 of 11 women who developed GDM relative to matched controls. We identified, for the first time, maternal methylation changes prior to the onset of GDM that may prove useful as biomarkers for early therapeutic intervention.