E. coli 4.5S RNA is part of a ribonucleoprotein particle that has properties related to signal recognition particle

E. coli 4.5S RNA and P48 have been shown to be homologous to SRP7S RNA and SRP54, respectively. Here we report that expression of human SRP7S in E. coli can suppress the lethality caused by depletion of 4.5S RNA. In E. coli, both RNAs are associated with P48. In vitro, both E. coli P48 and SRP54 specifically bind to 4.5S RNA. Strains depleted of 4.5S RNA strongly accumulate pre-beta-lactamase and fail to accumulate maltose binding protein. These effects commence well before any growth defect is observed and are suppressed by expression of human SRP7S. Strains overproducing P48 also accumulate pre-beta-lactamase. 4.5S RNA and P48 are components of a ribonucleoprotein particle that we propose to be required for the secretion of some proteins.     

The human anti-IL-1β monoclonal antibody ACZ885 is effective in joint inflammation models in mice and in a proof-of-concept study in patients with rheumatoid arthritis

Introduction

IL-1β is a proinflammatory cytokine driving joint inflammation as well as systemic signs of inflammation, such as fever and acute phase protein production.

Methods

ACZ885, a fully human monoclonal antibody that neutralizes the bioactivity of human IL-1β, was generated to study the potent and long-lasting neutralization of IL-1β in mechanistic animal models as well as in a proof-of-concept study in patients with rheumatoid arthritis (RA).

Results

The mouse IL-1 receptor cross-reacts with human IL-1β, and it was demonstrated that ACZ885 can completely suppress IL-1β-mediated joint inflammation and cartilage destruction in mice. This observation prompted us to study the safety, tolerability and pharmacodynamic activity of ACZ885 in RA patients in a small proof-of-concept study – the first to be conducted in humans. Patients with active RA despite treatment with stable doses of methotrexate were enrolled in this dose escalation study. The first 32 patients were split into four cohorts of eight patients each (six were randomly assigned to active treatment and two to placebo). ACZ885 doses were 0.3, 1, 3 and 10 mg/kg, administered intravenously on days 1 and 15. To explore efficacy within 6 weeks of treatment, an additional 21 patients were randomly assigned to the 10 mg/kg cohort, resulting in a total of 20 patients dosed with 10 mg/kg and 15 patients treated with placebo. There was clinical improvement (American College of Rheumatology 20% improvement criteria) at week 6 in the 10 mg/kg treatment group; however, this did not reach statistical significance (P = 0.085). A statistically significant reduction in disease activity score was observed after 4 weeks in the 10 mg/kg group. Onset of action was rapid, because most responders exhibited improvement in their symptoms within the first 3 weeks. C-reactive protein levels decreased in patients treated with ACZ885 within 1 week. ACZ885 was well tolerated. Three patients receiving ACZ885 developed infectious episodes that required treatment. No anti-ACZ885 antibodies were detected during the study.

Conclusion

ACZ885 administration to methotrexate-refractory patients resulted in clinical improvement in a subset of patients. Additional studies to characterize efficacy in RA and to determine the optimal dose regimen appear warranted.

Trial Registration

ClinicalTrials.gov identifier NCT00619905.     

Seasonal energetic constraints in Mediterranean benthic suspension feeders: effects at different levels of ecological organization

The aim of this work is to examine the role of food as a constraining factor at different levels of ecological organization in benthic littoral ecosystems. In the search for patterns in ecological systems, it has recently been documented that seasonality in the dynamics of benthic suspension feeders (BSF) in the Mediterranean Sea is characterized by summer dormancy. We review recent studies on seston availability in the water column and feeding and respiration by BSF in the Mediterranean. The objective is to assess whether a pattern across particular studies exists that could provide evidence of food as a constraining factor. A pattern emerges from these organism‐level studies, one which indicates the seasonal occurrence of an energy shortage in the taxa exhibiting summer dormancy. This energy shortage is closely related to low food availability and suggests that an energetic constraint underlie the summer dormancy phenomenon. The seasonal occurrence of summer energy shortage also appears to affect the dynamics of BSF at population and community level. In this sense, in late summer 1999, a mass mortality event of BSF affected several hundreds of kilometers in the Ligurian Sea (NW Mediterranean). The fact that the mass mortality event occurred in late summer and especially affected the taxa that exhibit energy shortage – such as anthozoans and sponges – suggests, that energetic constraints may contribute to the understanding of the mass mortality event. The energy shortage phenomenon may provide a mechanism to understand how the occurrence of anomalous climatic conditions may have induced the mass mortality of some BSF taxa. This review points out the existence of a common energy shortage phenomenon mainly related to low food availability as an important determinant of the dynamics of most BSF taxa at organism level in the Mediterranean. But this determinant also affects the dynamics of BSF at population and community level. Therefore, the extant data point up the crucial role of food as a constraining factor for benthic littoral ecosystems in oligotrophic areas like the Mediterranean, with important seasonal variations in seston abundance and composition.     

Circadian rhythm of glycoprotein secretion in the vas deferens of the moth, Spodoptera littoralis

Background  

Reproductive systems of male moths contain circadian clocks, which time the release of sperm bundles from the testis to the upper vas deferens (UVD) and their subsequent transfer from the UVD to the seminal vesicles. Sperm bundles are released from the testis in the evening and are retained in the vas deferens lumen overnight before being transferred to the seminal vesicles. The biological significance of periodic sperm retention in the UVD lumen is not understood. In this study we asked whether there are circadian rhythms in the UVD that are correlated with sperm retention.     

Recurrent partial mortality events in winter shape the dynamics of the zooxanthellate coral <Emphasis Type="Italic">Oculina patagonica</Emphasis> at high latitude in the Mediterranean

Global warming has many biological effects on corals and plays a central role in the regression of tropical coral reefs; therefore, there is an urgent need to understand how some coral species have adapted to environmental conditions at higher latitudes. We examined the effects of temperature and light on the growth of the zooxanthellate coral Oculina patagonica (Scleractinia, Oculinidae) at the northern limit of its distribution in the eastern Iberian Peninsula (western Mediterranean) by transplanting colonies onto plates and excluding them from space competition over a ~4-yr period. Each year, most of the colonies (~70%) exhibited denuded skeletons with isolated polyps persisting on approximately half of the coral surface area. These recurrent episodes of partial coral mortality occurred in winter, and their severity appeared to be related to colony exposure to cold but not to light. Although O. patagonica exhibited high resistance to stress, coral linear extension did not resume until the coenosarc regenerated. The resumption of linear extension was related to the dissociation of the polyps from the coenosarc and the outstanding regenerative capacity of this species (10.3 mm² d^?1). These biological characteristics allow the species to survive at high latitudes. However, the recurrent and severe pattern of denuded skeletons greatly affects the dynamics of the species and may constrain population growth at high latitudes in the Mediterranean.     

The beta2 integrin CD11c distinguishes a subset of cytotoxic pulmonary T cells with potent antiviral effects in vitro and in vivo

Background

The integrin CD11c is known as a marker for dendritic cells and has recently been described on T cells following lymphotropic choriomeningitis virus infection, a systemic infection affecting a multitude of organs. Here, we characterise CD11c bearing T cells in a murine model of localised pulmonary infection with respiratory syncytial virus (RSV).

Methods

Mice were infected intranasally with RSV and expression of β2 integrins and T lymphocyte activation markers were monitored by flow cytometry. On day 8 post RSV infection CD11c⁺ CD8⁺ and CD11c^- CD8⁺ T cells were assessed for cytokine production, cytotoxic activity and migration. Expression of CD11c mRNA in CD8⁺ T cells was assessed by quantitative PCR.

Results

Following RSV infection CD11c⁺ CD8⁺ T cells were detectable in the lung from day 4 onwards and accounted for 45.9 ± 4.8% of CD8⁺ T cells on day 8 post infection, while only few such cells were present in mediastinal lymph nodes, spleen and blood. While CD11c was virtually absent from CD8⁺ T cells in the absence of RSV infection, its mRNA was expressed in CD8⁺ T cells of both naïve and RSV infected mice. CD11c⁺, but not CD11c^-, CD8⁺ T cells showed signs of recent activation, including up-regulation of CD11a and expression of CD11b and CD69 and were recruited preferentially to the lung. In addition, CD11c⁺ CD8⁺ T cells were the major subset responsible for IFNγ production, induction of target cell apoptosis in vitro and reduction of viral titres in vivo.

Conclusion

CD11c is a useful marker for detection and isolation of pulmonary antiviral cytotoxic T cells following RSV infection. It identifies a subset of activated, virus-specific, cytotoxic T cells that exhibit potent antiviral effects in vivo.     

Fission yeast Sap1 protein is essential for chromosome stability

Sap1 is a dimeric sequence-specific DNA binding-protein, initially identified for its role in mating-type switching of the fission yeast Schizosaccharomyces pombe. The protein is relatively abundant, around 10,000 dimers/cell, and is localized in the nucleus. sap1⁺ is essential for viability, and transient overexpression is accompanied by rapid cell death, without an apparent checkpoint response and independently of mating-type switching. Time lapse video microscopy of living cells revealed that the loss of viability is accompanied by abnormal mitosis and chromosome fragmentation. Overexpression of the C terminus of Sap1 induces minichromosome loss associated with the “cut” phenotype (uncoupling mitosis and cytokinesis). These phenotypes are favored when the C terminus of Sap1 is overexpressed during DNA replication. Fluorescence in situ hybridization experiments demonstrated that the cut phenotype is related to precocious centromere separation, a typical marker for loss of cohesion. We propose that Sap1 is an architectural chromatin-associated protein, required for chromosome organization.