Protection against cartilage and bone destruction by systemic interleukin-4 treatment in established murine type II collagen-induced arthritis

Destruction of cartilage and bone are hallmarks of human rheumatoid arthritis (RA), and controlling these erosive processes is the most challenging objective in the treatment of RA. Systemic interleukin-4 treatment of established murine collagen-induced arthritis suppressed disease activity and protected against cartilage and bone destruction. Reduced cartilage pathology was confirmed by both decreased serum cartilage oligomeric matrix protein (COMP) and histological examination. In addition, radiological analysis revealed that bone destruction was also partially prevented. Improved suppression of joint swelling was achieved when interleukin-4 treatment was combined with low-dose prednisolone treatment. Interestingly, synergistic reduction of both serum COMP and inflammatory parameters was noted when low-dose interleukin-4 was combined with prednisolone. Systemic treatment with interleukin-4 appeared to be a protective therapy for cartilage and bone in arthritis, and in combination with prednisolone at low dosages may offer an alternative therapy in RA.     

Plant pathogens convergently evolved to counteract redundant nodes of an NLR immune receptor network

In plants, nucleotide-binding domain and leucine-rich repeat (NLR)-containing proteins can form receptor networks to confer hypersensitive cell death and innate immunity. One class of NLRs, known as NLR required for cell death (NRCs), are central nodes in a complex network that protects against multiple pathogens and comprises up to half of the NLRome of solanaceous plants. Given the prevalence of this NLR network, we hypothesised that pathogens convergently evolved to secrete effectors that target NRC activities. To test this, we screened a library of 165 bacterial, oomycete, nematode, and aphid effectors for their capacity to suppress the cell death response triggered by the NRC-dependent disease resistance proteins Prf and Rpi-blb2. Among 5 of the identified suppressors, 1 cyst nematode protein and 1 oomycete protein suppress the activity of autoimmune mutants of NRC2 and NRC3, but not NRC4, indicating that they specifically counteract a subset of NRC proteins independently of their sensor NLR partners. Whereas the cyst nematode effector SPRYSEC15 binds the nucleotide-binding domain of NRC2 and NRC3, the oomycete effector AVRcap1b suppresses the response of these NRCs via the membrane trafficking-associated protein NbTOL9a (Target of Myb 1-like protein 9a). We conclude that plant pathogens have evolved to counteract central nodes of the NRC immune receptor network through different mechanisms. Coevolution with pathogen effectors may have driven NRC diversification into functionally redundant nodes in a massively expanded NLR network.

Plant pathogens have evolved to counteract their hosts’ immune systems. A screen for pathogen effectors that suppress sensor NLR-mediated cell death in tobacco identifies effectors from a cyst nematode and an oomycete that suppress the NRC branch of the immune network to inhibit the immune-related cell death response.     

Fish chromatophores as cytosensors in a microscale device: detection of environmental toxins and bacterial pathogens

Fish chromatophores from Betta splendens are used as the cytosensor element in the development of a portable microscale device capable of detecting certain environmental toxins and bacterial pathogens by monitoring changes in pigment granule distribution. The adaptation of chromatophores to a microscale environment has required the development of enabling technologies to produce miniaturized culture chambers, to integrate microfluidics for sample delivery, to miniaturize image capture, and to design new statistical methods for image analyses. Betta splendens chromatophores were selected as the cytosensor element because of their moderate size, their toleration of close contact, and most importantly, for their responses to a broad range of chemicals and pathogenic bacteria. A miniaturized culture chamber has been designed that supports chromatophore viability for as long as 3 months, and that can be easily transported without damage to the cells. New statistical methods for image analyses have been developed that increase sensitivity and also decrease the time required for detection of significant changes in pigment granule distribution. Betta chromatophores have been tested for their responses to selected pathogenic bacteria and chemical agents. We discuss in detail the aggregation of pigment granules seen when chromatophores are incubated with Bacillus cereus, a common cause of food poisoning. Also described are the more subtle responses of chromatophores to a class of environmental chemical toxins, polynuclear aromatic hydrocarbons. We show that the chromatophores are able to detect the presence of certain polynuclear aromatic hydrocarbons at concentrations lower than the Environment Protection Agency (EPA) 550.1 standards.     

Going native,going local: revegetating eroded soils on the Falkland Islands using native seeds and farmland waste

Remote island ecosystems are vulnerable to human disturbance and habitat destruction, yet they often have limited capacity to revegetate degraded habitats, especially with native species. To revegetate degraded island habitats, practitioners often rely on importing non‐native species, thereby increasing the number of introduced species on islands. In this study, we investigated the effectiveness of sowing wild collected native seeds and locally sourced treatments for revegetating different eroded soil types (clay, peat, and sand) across the Falkland Islands. A seed mixture of 15 native species was sown with different supportive treatments (sheep dung, sheep dags [woolly off‐cuts], and geotextile matting [coir]) and their combinations. After 1 year, native seeds provided up to 70% plant cover and accrued 1.98 kg/m² in biomass. Three key native species Elymus magellanicus, Poa flabellata, and Poa alopecurus occurred in 64, 50, and 50% of all sown plots. However, supportive treatments equally facilitated the colonization and establishment of non‐native species. At the same time, there was no difference in native plant cover and biomass across different treatments or soil types, although in the absence of supportive treatments there was little to no revegetation. Thus, locally sourced treatments (i.e. sheep dung and dags) may provide an equally effective but low‐cost alternative to imported treatments (i.e. geotextiles). We further discuss challenges of integrating revegetation using native seeds and livestock grazing on the Falkland Islands. Our study demonstrates that native species and local treatments can provide a rapid approach to revegetating degraded island habitats.     

The phenotype and genotype of rheumatoid arthritis in the Democratic Republic of Congo

Introduction

Little is known about rheumatoid arthritis in the black, particularly in Congolese, populations. Our objective was to describe the phenotype and genotype of rheumatoid arthritis (RA) in Congolese.

Methods

All consecutive rheumatoid arthritis (RA) patients attending Kinshasa University Hospital in a three-year time period were included. Demographics, clinical features and tobacco consumption were noted. Disease Activity Score (DAS)-28 based on the erythrocyte sedimentation rate (ESR), Health Assessment Questionnaire (HAQ), anti-citrullinated peptide antibodies (CCP) antibodies and rheumatoid factor (RF) were determined. Radiographs were scored according to Sharp-van der Heijde. On a subset of patients and controls HLA-DRB1 typing was performed.

Results

A total of 114 females and 14 males aged 51.2 ± 14.9 were included. Mean duration of symptoms was four years. Moderate tobacco consumption was reported in a minority of patients. DAS-28 at first visit was >5.1 and HAQ ≥0.5 in all patients. X-rays showed joint erosions and/or joint space narrowing, mostly of a moderate grade in 55.8% of patients. Anti-CCP and/or RF were present in 48.6% of patients with available data (n = 72) and in 3.0% of controls (n = 67). Radiographic changes and nodules were more frequent in RF or anti-CCP positive patients. One copy of the shared epitope was found in 13 patients (35.1%) and 3 controls (12.5%). Two copies were found in one patient (2.7%) and in one control (4.2%).

Conclusion

Congolese patients with RA consult long after disease onset. Despite this delay, the majority presents without major damage and is RF, anti-CCP and SE negative. We put forward the hypothesis that besides different environmental factors there is probably also a particular genetic risk profile in Congolese patients, different from the HLA-DRB1 shared epitope.     

The DNA-binding domain of simian virus 40 tumor antigen has multiple functions.

The DNA-binding domain of simian virus 40 tumor antigen has been previously shown to participate in a number of different activities. Besides being involved in binding to sequences at the viral replication origin, this domain appears to be required for nonspecific DNA binding, for structurally distorting origin DNA (melting and untwisting), and possibly for oligomerization of the protein into hexamers and double hexamers. We now provide evidence that it also takes part in unwinding origin DNA sequences, contributes a function specifically related to in vivo DNA replication, and perhaps supports the assembly of the virus or release of the virus from the cell. This 100-amino-acid domain appears to be an excellent model system for studying how a small region of a protein could have a number of distinct activities.     

Subcellular localization of DNA-binding protein BA by immunofluorescence and immunoelectron microscopy

Nonhistone protein BA has been shown to decrease in amount in the chromatin of growth- stimulated normal rat liver (Yeoman et al. 1975. Cancer Res. 35:1249-1255) and in mitogen-stimulated normal human lymphocytes (Yeoman et al. 1976. Exp. Cell Res. 100:47- 55.). Subsequently, protein BA was purified and was shown to prefer to bind to double- stranded A-T-rich DNAs (Catino et al. 1978. Biochemistry. 17:983-987.). Immunization of rabbits with highly purified protein BA has resulted in the production of a specific antibody. A specific immunoreactivity for chromosomal protein BA has been demonstrated by immunoelectrophoresis and double antibody immunoprecipitation analysis with rabbit anti-BA immunoglobulin and IgG fractions. Light microscope examination of normal rat liver crysections by the indirect immunofluorescence procedure has demonstrated a cytoplasmic as well as a nuclear localization for protein BA with a pronounced perinucleolar fluorescence. Immunoelectron microscopy employing the peroxidase antiperoxidase method of antigen localization has confirmed the immunofluorescence data and has show a heterochromatin localization for protein BA. The relationship of the localization of protein BA to gene control in quiescent cells or to configurations of heterochromatin as well as the marked reduction in the amounts of protein BA which occur in stimulated growth states remains to be defined.