A Secreted Form of the Asialoglycoprotein Receptor, sH2a, as a Novel Potential Noninvasive Marker for Liver Fibrosis

Background and Aim: The human asialoglycoprotein receptor is a membrane heterooligomer expressed exclusively in hepatocytes. A soluble secreted form, sH2a, arises, not by shedding at the cell surface, but by intracellular cleavage of its membrane-bound precursor, which is encoded by an alternatively spliced form of the receptor H2 subunit. Here we determined and report that sH2a, present at constant levels in serum from healthy individuals is altered upon liver fibrosis, reflecting the status of hepatocyte function. Methods: We measured sH2a levels in serum using a monoclonal antibody and an ELISA assay that we developed, comparing with routine liver function markers. We compared blindly pretreatment serum samples from a cohort of 44 hepatitis C patients, which had METAVIR-scored biopsies, with 28 healthy individuals. Results: sH2a levels varied minimally for the healthy individuals (150621 ng/ml), whereas the levels deviated from this normal range increasingly in correlation with fibrosis stage. A simple algorithm combining sH2a levels with those of alanine aminotransferase allowed prediction of fibrosis stage, with a very high area under the ROC curve of 0.86

Strip clay application accelerates for 15–20 years the vegetation formation in ash dump (Middle Urals, Russia)

As a result of a generalization of 45-year monitoring observations at on the ash dump of the Verkhniy Tagil Power Station, the absolute time scale was made, stabilization rates during succession of different plant communities characteristics were assessed in two areas: recultivated and non-recultivated. Recultivation consisted of clay strips applying (5–8 m wide, 10–15 cm thick) on ash surface. All characteristics of plant communities (total projective cover by plants, total number of species in plant community) are formed 15–20 years faster in recultivated area. So, a simple technical recultivation, (clay strips applying), significantly accelerates the formation of plant communities main characteristics on ash surface in subzone of the southern taiga in Middle Urals

Constant serum levels of secreted asialoglycoprotein receptor sH2a and decrease with cirrhosis

AIM: To investigate the existence and levels of sH2a, a soluble secreted form of the asialoglycoprotein receptor in human serum

Invasibility of Common Plant Community Types of the Middle Urals

This paper specifies the invasibility of common plant community types in the natural habitats of the Middle Urals. Invasibility was defined as the vulnerability of a community to alien plant species invasions, regardless of the conditions in which the community existed. We analyzed 749 vegetation relevés made in natural bogs, floodplains, rocky grasslands, meadows, and forest communities. We surveyed urban and non-urban habitats (30–40 km from the city). Invasibility was calculated in two different ways based on two parameters: the number and proportion of alien species in the relevé. These invasibility parameters are widely applicable and comparable, scale-independent, measurable, and reliable, based on data that do not require the destruction of ecosystems or biota and are based on available data. Based on the invasibility degree, we identified three community-type groups with two subgroups in one group. In ascending order of invasibility degree, the community types were arranged as follows: (1) bogs with and without trees; (2a) coniferous forests; grass communities in floodplains; (2b) deciduous forests, coniferous plantations, floodplain communities with woody plants; and (3) dry meadows and rocky grasslands. Obtained results of the assessment of different plant community invasibility may be used to understand patterns of alien plant distribution in local habitats and the reasons for the different vulnerability of communities to plant invasions

Healthy individuals.

<p>Healthy individuals.</p

HCV patients.

1<p>Median of absolute values divided by upper limit of normal range.</p

ROC plots of sH2a and of the combination score of sH2a and ALT.

<p><b>A</b>) Receiver operating characteristic (ROC) plot of sH2a values for advanced fibrosis and cirrhosis (METAVIR 0–1 vs 3–4) for the group of 44 HCV patients. <b>B–C</b>) ROC plots of the combined scores of sH2a and ALT were made for advanced fibrosis and cirrhosis (METAVIR 0–1 vs 3–4) (B) or for intermediate fibrosis (METAVIR 0–1 vs 2–3) (C) of the same group of patients.</p

Model depicting the sequence of events in the fibrogenic process and changes in sH2a secretion.

<p>The membrane-bound precursor of sH2a is cleaved in the endoplasmic reticulum of healthy hepatocytes, traverses the secretory pathway and is secreted to the plasma (step 1). As a consequence of HCV infection and possibly also upon other insults, hepatocytes are damaged, their overall function is compromised and sH2a secretion is reduced, while intracellular enzymes like ALT are released to the plasma (step 2). This starts a process of inflammation (step 3), activation of hepatic stellate cells leading to fibrosis and then cirrhosis, which involve secretion and progressive accumulation of ECM components (step 4).</p

Univariate analysis of correlation of characteristics with advanced fibrosis.

1<p>Data is presented as n (%) except for age, which is presented as median (IQR); odds ratios are from simple logistic regression, using the forced entry method, on each variable. The dependent variable in the regression is state and the outcome is METAVIR score (1 if state is 3–4); CI, confidence interval presented for each explanatory variable.</p