Small regulatory RNAs may sharpen spatial expression patterns

The precise establishment of gene expression patterns is a crucial step in development. Formation of a sharp boundary between high and low spatial expression domains requires a genetic mechanism that exhibits sensitivity, yet is robust to fluctuations, a demand that may not be easily achieved by morphogens alone. Recently, it has been demonstrated that small RNAs (and, in particular, microRNAs) play many roles in embryonic development. Whereas some RNAs are essential for embryogenesis, others are limited to fine-tuning a predetermined gene expression pattern. Here, we explore the possibility that small RNAs participate in sharpening a gene expression profile that was crudely established by a morphogen. To this end, we study a model in which small RNAs interact with a target gene and diffusively move from cell to cell. Though diffusion generally smoothens spatial expression patterns, we find that intercellular mobility of small RNAs is actually critical in sharpening the interface between target expression domains in a robust manner. This sharpening occurs as small RNAs diffuse into regions of low mRNA expression and eliminate target molecules therein, but cannot affect regions of high mRNA levels. We discuss the applicability of our results, as examples, to the case of leaf polarity establishment in maize and Hox patterning in the early Drosophila embryo. Our findings point out the functional significance of some mechanistic properties, such as mobility of small RNAs and the irreversibility of their interactions. These properties are yet to be established directly for most classes of small RNAs. An indirect yet simple experimental test of the proposed mechanism is suggested in some detail.     

Paraoxonase-1 activity in patients with hyperemesis gravidarum

There is increasing evidence that oxidative stress may play a role in the pathophysiology of hyperemesis gravidarum. Serum paraoxonase-1 (PON-1) is a high density lipoprotein (HDL)-associated enzyme that prevents oxidative modification of low density lipoprotein. The aim of the study was to measure the serum levels of PON-1 activity in women with hyperemesis gravidarum. Thirty-four women with hyperemesis gravidarum and 31 healthy pregnant women were enrolled in the study. Serum PON-1 activity was measured spectrophotometrically. Lipid hydroperoxide (LOOH) levels were measured by iodometric assay. PON-1 activity was significantly lower and LOOH levels were significantly higher in pregnant women with hyperemesis gravidarum than in healthy pregnant women (P < 0.0001, for all). There were significant correlations between PON-1 and LOOH, triglyceride, total cholesterol, HDL, low density lipoprotein (LDL) and high sensitive C-reactive protein (HSCRP; P < 0.0001, for all). By using multiple regression analysis LDL, HDL, HSCRP and LOOH were independent determinants of serum PON-1 activity in the study. Decreased PON-1 activity might be related to increased oxidative stress and inflammation in pregnant women with hyperemesis gravidarum. Subjects with hyperemesis gravidarum might be more prone to the development of atherogenesis due to low serum PON-1 activity.     

Effect of sulfite treatment on total antioxidant capacity, total oxidant status, lipid hydroperoxide, and total free sulfydryl groups contents in normal and sulfite oxidase-deficient rat plasma

Sulfites, which are commonly used as preservatives, are continuously formed in the body during the metabolism of sulfur-containing amino acids. Sulfite oxidase (SOX) is an essential enzyme in the pathway of the oxidative degradation of sulfite to sulfate protecting cells from sulfite toxicity. This article investigated the effect of sulfite on total antioxidant capacity (TAC), total oxidant status, lipid hydroperoxide (LOOH), and total free sulfydryl groups (-SH) levels in normal and SOX-deficient male albino rat plasma. For this purpose, rats were divided into four groups: control, sulfite-treated, SOX-deficient, and sulfite-treated SOX-deficient groups. SOX deficiency was established by feeding rats a low molybdenum diet and adding to their drinking water 200 ppm tungsten. Sulfite (70 mg/kg) was administered to the animals via their drinking water. SOX deficiency together with sulfite treatment caused a significant increase in the plasma LOOH and total oxidant status levels. -SH content of rat plasma significantly decreased by both sulfite treatment and SOX deficiency compared to the control. There was also a significant decrease in plasma TAC level by sulfite treatment. In conclusion, sulfite treatment affects the antioxidant/oxidant balance of the plasma cells of the rats toward oxidants in SOX-deficient groups.     

Alterations of serum selenium, zinc, copper, and iron concentrations and some related antioxidant enzyme activities in patients with cutaneous leishmaniasis

The aim of this study was to measure the alterations in serum selenium (Se), copper (Cu), zinc (Zn), and iron (Fe) concentrations and their carrier proteins, ceruloplasmin (Cp), transferrin (Tf) albumin, and related antioxidant enzyme activities, erythrocyte Cu-Zn Superoxide dismutase (Cu-Zn SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities in patients with cutaneous leishmaniasis (CL). Erythrocyte Cu-Zn SOD activities, serum Cu concentrations, and Cp levels were found to be significantly higher in the patients group than those of controls. However, GSH-Px and CAT activities and Se, Zn, Fe, and Tf levels were lower in patients than in the control subjects. There were positive important correlation’s between Cu-Zn SOD and Cp, Cu-Zn SOD and Cu, Cp and Cu, GSH-Px and Se, and Fe and CAT in the patients group. Our results showed that serum essential trace elements Se, Zn, Cu, and Fe concentrations and their related enzymes Cu-Zn SOD, GSH-Px, and CAT activities change in CL patients. The changes may be a part of defense strategies of organism and are induced by the hormonelike substances.     

Increased DNA damage in patients with complete hydatidiform mole

The pathologic mechanisms underlying the gestational trophoblastic diseases are largely unexplored, but are thought to involve oxidative damage to the maternal vasculature and also to the placenta. In this study we have assessed the plasma levels of total antioxidant response (TAR) and the levels of endogenous DNA damage--determined by the comet assay--in peripheral blood lymphocytes from 13 women with complete hydatidiform mole (CHM) and compared these with those of 12 healthy pregnant controls and 10 healthy non-pregnant controls. Significantly lower mean levels of plasma TAR were found in patients with CHM compared with healthy pregnant controls (1.08+/-0.29 versus 1.17+/-0.14 mmol Trolox Eq/L, p<0.05) and with healthy non-pregnant controls (1.08+/-0.29 versus 1.38+/-0.12 mmol Trolox Eq/L, p<0.05). Significantly higher mean levels of endogenous DNA damage were observed in patients with CHM than in healthy pregnant controls (234.5+/-50.74 versus 125.7+/-45.4 AU, p<0.05) or in healthy non-pregnant controls (234.5+/-50.74 versus 104.0+/-49.6 AU, p<0.05). We observed an inverse correlation between the plasma TAR and the levels of endogenous DNA damage (r=-0.64, p<0.01), in that the levels of oxidative damage to the DNA were found to parallel the decrease in the plasma TAR in the CHM group. These results reveal a relationship between the extracellular and intracellular (as reflected by damage to the DNA) levels of oxidation. Our observations suggest that there is a link between the increased levels of oxidative stress and the increase in endogenous DNA damage seen in patients with CHM, as compared with those seen in normal pregnancy. However, the nature of this link, and whether it is direct or indirect, remains to be explored.     

Small RNA biology is systems biology

During the last decade small regulatory RNA (srRNA) emerged as central players in the regulation of gene expression in all kingdoms of life. Multiple pathways for srRNA biogenesis and diverse mechanisms of gene regulation may indicate that srRNA regulation evolved independently multiple times. However, small RNA pathways share numerous properties, including the ability of a single srRNA to regulate multiple targets. Some of the mechanisms of gene regulation by srRNAs have significant effect on the abundance of free srRNAs that are ready to interact with new targets. This results in indirect interactions among seemingly unrelated genes, as well as in a crosstalk between different srRNA pathways. Here we briefly review and compare the major srRNA pathways, and argue that the impact of srRNA is always at the system level. We demonstrate how a simple mathematical model can ease the discussion of governing principles. To demonstrate these points we review a few examples from bacteria and animals.