Effect of heparin contained in preparations of small cytoplasmic RNAs on cell-free translation.

It has been reported that small cytoplasmic RNA (scRNA) from human placenta inhibits translation of most mRNAs in both wheat germ extracts and reticulocyte lysates (Lorberboum, H., Digweed, M., Erdmann, V. A., Servadio, Y., Weinstein, D., De Groot, N., and Hochberg, A. A. (1986) Eur. J. Biochem. 155, 279-287). We have investigated the mechanism by which scRNA preparations inhibit mRNA translation in vitro. We demonstrate that the inhibitory agent(s) is not sensitive to treatment with various ribonucleases but that translational inhibition is sensitive to incubation with 1 N NaOH at 95 degrees C or to treatment with heparinase. Based on these findings and on the ability of heparin to inhibit cell-free translation by itself, we conclude that the presence of heparin in preparations of scRNA from human placenta is responsible for effects which have previously been attributed to inhibitory RNA molecules. Since heparin is also frequently used in the isolation of translationally inhibitory scRNAs from other sources, we suggest that the sensitivity of these preparations to ribonucleases and heparinase should be examined.     

Human adipose tissue under in vitro inhibition of 11beta-hydroxysteroid dehydrogenase type 1: differentiation and metabolism changes.

In humans, oxoreducing 11beta-HSD-1 activity appears to be related to body fat distribution in male-type central obesity, but not in female-type peripheral obesity. We postulated that inhibition of 11beta-HSD-1 might have clinical therapeutic significance in oxoreducing mostly visceral fat and its metabolic activity. Our current study investigated the consequence at the cellular level of such inhibition. As an inhibitor of 11beta-HSD-1 activity, we used the licorice derivative carbenoxolone. Carbenoxolone has an inhibitory effect on the activity of both oxidizing 11beta-HSD-2, which converts cortisol to cortisone, and oxoreducing 11beta-HSD-1; yet, preadipocytes and adipocytes only express the latter. Preadipocytes were retrieved from omental and subcutaneous fat from healthy non-obese individuals and differentiated in vitro to mature adipocytes. Activity of 11beta-HSD-1 was assayed by measuring conversion of added 500 nM cortisone to cortisol. Expression of 11beta-HSD-1 mRNA was determined by real-time PCR, while lipolytic effects were determined by measuring glycerol and triglyceride concentration in the culture medium. Carbenoxolone decreased 11beta-HSD-1 activity in a dose-dependent manner with an IC-50 of 5X10 -6 M, but did not affect the expression of 11beta-HSD-1 mRNA. Cortisone stimulated subcutaneous, but not omental preadipocytes proliferation, an effect that was not abolished by carbenoxolone. Dexamethasone had a stimulatory effect on the maturation of both omental and subcutaneous preadipocytes. Carbenoxolone per se, either with or without cortisone, had a negative effect on preadipocyte maturation. Inhibiting 11beta-HSD-1 activity by carbenoxolone had no impact on leptin secretion. Thus, carbenoxolone has no effect on preadipocyte proliferation, but a dramatic inhibitory effect on preadipocyte differentiation into mature adipocytes. The mechanism is only partly related to its inhibitory effect on 11beta-HSD-1 activity. The present observations lend support to the presence of an intracrine loop of a hormone that is both produced from a precursor and active within the preadipocyte and adipocyte.     

Elemental characterization of the exoskeleton in the whipscorpions Mastigoproctus giganteus and Typopeltis dalyi (Arachnida: Thelyphonida)

The arthropod cuticle is a structurally diverse secretion that is largely composed of lipids, proteins, and α‐chitin that function together in protection, prey capture, and as a skeletal framework for efficient and diverse means of locomotion. Aquatic, aerial, and terrestrial arthropods are well known to enrich their cuticles with trace elements that are proposed to strengthen or otherwise enhance specific regions of the exoskeleton. In this study, we provide evidence that whipscorpions (vinegaroons) enrich their exoskeleton with up to 14 trace elements. We use energy‐dispersive x‐ray spectroscopy (EDS) to provide the first comparisons of trace element composition in two species of Thelyphonida: Mastigoproctus giganteus (female) and Typopeltis dalyi (female and male). We analyzed the chemical composition of eight regions that have sensory, locomotory, taxonomic, protective, and/or predatory significance: the flagellum, prosoma, tarsal claws of the walking legs, tarsi of the antenniform legs, chelicerae, and the terminal three segments of the pedipalps. Our results reveal the presence of 14 trace elements across both species (12 elements in T. dalyi, 10 elements in M. giganteus), and only four elements are present at significant levels (≥1% weight): Si, Cl, Ca, and Zn. The flagellum, antenniform leg tarsi, and prosoma keel lack these elements in both species, while the chelicerae of all species are enriched with Ca, Zn, and Cl, and the tarsal claws are enriched with Zn. Significantly, we note the presence of Si in the prosomal carapace (but not the keel) of males and females of Typopeltis only, which appears to be the first evidence of this transition metal in the arthropod exoskeleton. We discuss the significance of these chemical enrichments in whipscorpions and provide hypotheses about their functional significance.     

A meta-analysis of the incidence of malignancy in adult patients with rheumatoid arthritis

Introduction

The risk of malignancies in patients with rheumatoid arthritis (RA) has raised some concern, particularly with immunosuppressive approaches to disease management.

Methods

We conducted a systematic review of the literature and meta-analysis characterizing the associated risk of overall malignancy and four site-specific malignancies (lymphoma, lung, colorectal, and breast cancer) in patients with RA. A Medline search from 1990 to 2007 was conducted using specified search terms and predefined inclusion criteria for identification of relevant observational studies that provide estimates of relative risk of malignancy associated with RA. Study-specific estimates of the relative risk, as measured by standardized incidence ratios (SIRs) and estimated in comparison with the general population, were combined using a random effects model.

Results

A total of 21 publications were identified, of which 13 reported the SIR for overall malignancy, 14 for lymphoma, 10 for colorectal, 12 for lung, and 9 for breast cancer. Compared with the general population, the overall SIR estimates suggest that RA patients have approximately a two-fold increase in lymphoma risk (SIR 2.08, 95% confidence interval [CI] 1.80 to 2.39) and greater risk of Hodgkin than non-Hodgkin lymphoma. The risk of lung cancer was also increased with an SIR of 1.63 (95% CI 1.43 to 1.87). In contrast, a decrease in risk was observed for colorectal (SIR 0.77, 95% CI 0.65 to 0.90) and breast (SIR 0.84, 95% CI 0.79 to 0.90) cancer. The SIR for overall malignancy was 1.05 (95% CI 1.01 to 1.09).

Conclusion

Patients with RA appear to be at higher risk of lymphoma and lung cancer and potentially decreased risk for colorectal and breast cancer compared with the general population.     

The evolutionary ecology of metacommunities

Research on the interactions between evolutionary and ecological dynamics has largely focused on local spatial scales and on relatively simple ecological communities. However, recent work demonstrates that dispersal can drastically alter the interplay between ecological and evolutionary dynamics, often in unexpected ways. We argue that a dispersal-centered synthesis of metacommunity ecology and evolution is necessary to make further progress in this important area of research. We demonstrate that such an approach generates several novel outcomes and substantially enhances understanding of both ecological and evolutionary phenomena in three core research areas at the interface of ecology and evolution.     

Virulence and age at reproduction: new insights into host–parasite coevolution

We consider an explicit mutation–selection process to investigate the dynamics underlying the coevolution of parasite’s virulence and host’s prereproductive life span in a system with discrete generations. Conforming with earlier models, our model predicts that virulence generally increases with natural mortality of the host, and that a moderate increase in virulence selects for lower ages at reproduction. However, the epidemiological feedback in our model also gives rise to unusual and unexpected patterns. In particular, if virulence is sufficiently high the model can lead to a bifurcation pattern, where two strategies coexist in the host population. The first is to develop rapidly to reproduce before being infected. Individuals following this strategy suffer, however, from reduced fecundity. The second strategy is to develop much more slowly. Because of the high virulence, the effective period of transmission is short, so that a few slowly developing individuals escape infection. These individuals, although choosing a risky strategy, benefit from high fecundity.     

The musculature of Draculiciteria tessalata (Chaetonotida, Paucitubulatina): implications for the evolution of dorsoventral muscles in Gastrotricha

The muscular system of the marine interstitial gastrotrich Draculiciteria tessalata (Chaetonotida, Paucitubulatina) was analyzed with fluorescent phalloidin. Muscles in circular, longitudinal, helicoidal and dorsoventral orientations were found. Circular muscles were present as discreet rings on the pharynx only. Five pairs of longitudinal muscles were found in dorsal, lateral and ventral positions. One of the two pairs of lateral muscles is newly described for the species. Helicoidal muscles, external to the circular muscles and some longitudinal bands, spiraled around the pharynx and anterior portion of the intestine. Two pairs of segmentally-arranged dorsoventral muscles were also present. Lateral dorsoventral muscles extended from the base of the pharynx to the anterior part of the caudal furca. Medial dorsoventral muscles extended from the pharyngeal-intestinal junction into each ramus of the caudal furca. A hypothesis on the evolution of dorsoventral muscles in D. tessalata is proposed which includes a splitting of circular muscles into separate somatic and splanchnic components with a further displacement of both muscle sets into a dorsoventral orientation.     

The muscular system of Dactylopodola baltica and other macrodasyidan gastrotrichs in a functional and phylogenetic perspective

The gastrotrich muscular system is characterized by band-like muscles arranged in orientations that reflect both function and phylogeny. To better understand the evolution of the Dactylopodolidae, a putative primitive lineage and potential sister group to other extant macrodasyidans, we have used a fluorescent phalloidin stain to visualize muscle patterns in the marine gastrotrich Dactylopodola baltica and eight other species of Macrodasyida from four families. The musculature of D. baltica is arranged as a series of circular, helicoidal and longitudinal bands around the digestive tract. Circular muscles and longitudinal muscles were found in splanchnic and somatic positions. Helicoidal muscles, in 50–60° angles with respect to the longitudinal body axis, surrounded circular and longitudinal splanchnic muscles in a spiralling orientation. The largest longitudinal muscles were the ventrolateral bands composed of numerous cross-striated myocytes arranged in parallel arrays. The overall arrangement of the muscular system of D. baltica showed several similarities to other macrodasyidan gastrotrichs, including the presence and location of circular, helicoidal and longitudinal muscles, their orientation with respect to the longitudinal body axis and their points of insertion. Unique to D. baltica is the anterior and posterior arrangement of the ventrolateral muscles and the orientation of muscle branches that supply the ventral and dorsal aspects of the pharynx. Muscle data from observations of D. baltica and eight additional species were coded as phylogenetic characters, mapped onto a cladogram and compared to an existing phylogeny of the order. The direction of evolutionary change in specific muscle groups was inferred, as was the ground pattern of muscles for the Macrodasyida.     

Functional morphology of muscles in Tetranchyroderma papii (Gastrotricha)

Movement in gastrotrichs is powered by an interaction of ventral cilia and muscles. In interstitial gastrotrichs, movement among sand grains often requires the additional use of adhesive tubules that allow for behaviors such as escape responses and changes in body position. In this study, we describe orientations and possible mechanical actions of muscles during locomotion in the gastrotrich, Tetranchyroderma papii (Macrodasyida). Fluorescently labeled phalloidin was used to stain F-actin of muscles and visualize muscle patterns. Muscles are arranged in circular, longitudinal, and helicoidal orientations. Circular muscles were in the form of discreet rings around the pharynx and intestine, and contribute to the structure of the oral hood. Longitudinal muscles are largely concentrated on the ventral and ventrolateral sides of the body, where they aid in body flexion, including directional changes during ciliary swimming, body torsion, and escape responses. Helicoidal muscles, present as myocytes in left- and right-hand orientations, lie external of the circular bands and some of the longitudinal bands, and are hypothesized to counteract dilations of the pharynx and intestine during feeding. Extraordinary muscle orientations with undetermined functions include a pair of crossover muscles and a single semicircular muscle band at the caudal end. Accepted: 12 February 2001