Expression of Three Gastrula Cell Surface Glycoproteins during Embryonic and Larval Development in the Amphibian Pleurodeles waltlii

We have previously reported the identification of cell surface glycoproteins in Pleurodeles waltlii gastrulae. In an attempt to study the expression of three of these cell surface glycoproteins (proteins referred to 1, 11 and 14), we have produced monoclonal and polyclonal antibodies by immunizing mice with the spots of the three selected glycoproteins excised from 2D-gels. Expression of the three glycoproteins was detected on the surfaces of all cells during embryonic development. Before hatching, proteins 1, 11 and 14 become expressed in a limited number of tissues.     

Polymorphism: a weak influence on worker aggregation level in ants

Abstract.  1. Aggregation of individuals, a basic behaviour in social species, plays an essential role in many aspects of animal life (reproduction, defence, and alimentation). Understanding how this phenomenon is modulated is important to comprehend the social organisation of the group.
2. In social insects, aggregation is influenced by environmental (e.g. the light level) and social (e.g. polyethism in monomorphic ants) factors. Ants display a great variation of biological characteristics (e.g. queen number, polymorphism, division of labour, etc.) that are likely to influence the level of inter-attraction and so the aggregation.
3. The present research focused on one biological characteristic: the morphological castes (minors, majors), testing the hypothesis that minors will aggregate more than majors due to their greater need to fight against the loss of heat and to increase their self-protection.
4. Aggregation experiments were conducted on two highly polymorphic species, Atta sexdens rubropilosa and Solenopsis interrupta , using the two extreme morphological castes (majors and minors).
5. All castes exhibited a low level of aggregation: 40–50% of workers assembled for both species, the biggest cluster involving 20% of the total population. The lack of difference between morphological castes in the aggregation shows the weak influence of polymorphism on the interactions between ants.
6. It is concluded that the main factor modulating the aggregation behaviour is polyethism, i.e. the division of labour associated with the presence of an outside-the-nest experience: workers that only take care of the brood, without outside world experience (brood-tenders) assembling more than foraging workers (foragers).     

Asymmetrical costs of sexual conflict in the seaweed fly, Coelopa frigida

Abstract.  1. Sexual conflict can play an important role in the evolution of animal life-history characteristics, including lifespan. Seaweed flies show an increase in mortality rates when exposed to brown algae. The seaweed stimulates females to oviposit and males to mount females. Females typically respond to male mounts by performing a violent rejection response.
2. Here the contribution of sexual conflict to the increase in mortality seen in the presence of seaweed was determined. The survival of single and mixed sex pairs of flies was followed in the presence and absence of seaweed.
3. The two sexes showed differential survival rates, with females living longer in the absence of seaweed. The presence of seaweed reduced survival in both sexes. In the presence of seaweed, female survival was lower when paired with a male. Over 40% of the reduction in survival in females in the presence of seaweed appears to be attributable to sexual conflict.
4. The presence of a female did not significantly affect male survival. Thus the mortality cost of being in the presence of the opposite sex and seaweed appears highly asymmetric.
5. In the presence of seaweed, female survival was lower when females were paired with small males. Small males exhibit higher levels of harassment of females, thus it is argued that pre-copulatory sexual conflict is the probable cause of the increased mortality cost to females of being in the presence of both males and seaweed.     

Immature dendritic cells suppress collagen-induced arthritis by in vivo expansion of CD49b+ regulatory T cells

Dendritic cells (DCs) are specialized APCs with an important role in the initiation and regulation of immune responses. Immature DCs (iDCs) reportedly mediate tolerance in the absence of maturation/inflammatory stimuli, presumably by the induction of regulatory T cells. In this study, we show for the first time that repetitive iDC injections trigger the expansion of a novel regulatory population with high immunomodulatory properties, able to protect mice from collagen-induced arthritis. These regulatory T cells are characterized by the expression of the CD49b molecule and correspond to a CD4+ alpha-galactosylceramide/CD1d-nonrestricted T cell population producing IL-10. Adoptive transfer of < 10(5) TCRbeta+ CD49b+ cells isolated from the liver of iDCs-vaccinated mice, conferred a complete protection against arthritis. This protection was associated with an attenuation of the B and T cell response associated with a local secretion of IL-10. Thus, together these data demonstrate that iDCs can expand and activate a novel regulatory population of CD49b+ T cells, with high immunosuppressive potential able to mediate protection against a systemic autoimmune disease.     

ACPA fine-specificity profiles in early rheumatoid arthritis patients do not correlate with clinical features at baseline or with disease progression

Introduction

Autoantibodies against citrullinated peptides/proteins (ACPA) are found in approximately 75% of the sera of patients with rheumatoid arthritis (RA). The RA-specific ACPA are frequently present prior to disease onset and their presence associates with a more erosive disease course. ACPA can therefore be used to aid the diagnosis and prognosis of RA. Recently, it became clear that ACPA are very heterogeneous, both in an individual patient and among different patients. The aim of this study was to investigate whether clinically meaningful ACPA profiles exist in early RA patients.

Methods

Twenty citrullinated peptides and the corresponding non-citrullinated control peptides were immobilized on microarray sensor chips. Sera from 374 early arthritis patients were analyzed by surface plasmon resonance imaging (iSPR) of biomolecular interactions on the sensor chip.

Results

Cluster analysis of the reactivities with the citrullinated peptides, after subtraction of the reactivities with the corresponding control peptides confirmed the heterogeneity of the ACPA response in RA and revealed 12 distinct ACPA profiles. The association of the 5 most frequent profiles with clinical features at diagnosis and during the disease course was examined, showing no statistically significant associations.

Conclusions

Compared to the detection of ACPA in RA sera by CCP-based assays, ACPA profiling in early arthritis patients did not reveal associations with disease activity and progression scores.     

Characterization of Heavy Metal Resistance of Metal-Reducing Shewanella Isolates From Marine Sediments

This study focuses on heavy metal resistance of marine, benthic Mn(IV)- and Fe(III)-reducing bacteria and their potential to mobilize heavy metals from sedimentary phases, as hydrous ferric oxides (HFO) and Mn(IV)-oxides (δ -MnO ₂ ). One isolate was obtained from enrichments of metal-polluted sediment with δ -MnO ₂ (strain MB4, 99% similarity to S. marisflavi), and two strains were isolated from enrichments on HFO (strain FB18 and FS8, 98 and 97% 16S rRNA gene similarity to Shewanella collwelliana). The 16S rRNA sequences similar to isolates MB4 and FS8 were detected previously in DGGE profiles and clone libraries of the original sediment samples. Toxicity tests under aerobic conditions showed that the latter two ceased growth at 150 μ M Cu, but strain MB4 and reference strain S. oneidensis MR1 were more tolerant to copper; growth with 150 μ M Cu reached 56–58 ± 0.1% of maximal optical density, OD_max, in control cultures. Similar experiments conducted under anaerobic conditions with fumarate indicated no significant change in copper tolerance in strain MB4 (66 ± 3% OD_max at 150 μ M). Biphasic experiments with δ -MnO ₂ -reduction followed by use of fumarate, furthermore indicated that the presence of manganese oxides decreased bio-availability of copper through sorption processes, thereby alleviating the toxicity of copper to strain MB4 to some extent. Scanning electron microscopic images showed the initial amorphous Mn(IV)-oxides and newly formed, highly crystalline, lemon-shaped, particles making up the precipitate that remained after microbial reduction. Concomitant electron dispersive x-ray spectrometry confirmed presence of copper in the initial sample, yet detected no copper in the precipitate after microbial reduction, indicating that the Mn(IV)-reducing Shewanella strain MB4 mobilized copper adsorbed to δ -MnO ₂ .     

Interaction analysis between HLA-DRB1 shared epitope alleles and MHC class II transactivator CIITA gene with regard to risk of rheumatoid arthritis

HLA-DRB1 shared epitope (SE) alleles are the strongest genetic determinants for autoantibody positive rheumatoid arthritis (RA). One of the key regulators in expression of HLA class II receptors is MHC class II transactivator (CIITA). A variant of the CIITA gene has been found to associate with inflammatory diseases.We wanted to explore whether the risk variant rs3087456 in the CIITA gene interacts with the HLA-DRB1 SE alleles regarding the risk of developing RA. We tested this hypothesis in a case-control study with 11767 individuals from four European Caucasian populations (6649 RA cases and 5118 controls).We found no significant additive interaction for risk alleles among Swedish Caucasians with RA (n = 3869, attributable proportion due to interaction (AP) = 0.2, 95%CI: −0.2–0.5) or when stratifying for anti-citrullinated protein antibodies (ACPA) presence (ACPA positive disease: n = 2945, AP = 0.3, 95%CI: −0.05–0.6, ACPA negative: n = 2268, AP = −0.2, 95%CI: −1.0–0.6). We further found no significant interaction between the main subgroups of SE alleles (DRB1*01, DRB1*04 or DRB1*10) and CIITA. Similar analysis of three independent RA cohorts from British, Dutch and Norwegian populations also indicated an absence of significant interaction between genetic variants in CIITA and SE alleles with regard to RA risk.Our data suggest that risk from the CIITA locus is independent of the major risk for RA from HLA-DRB1 SE alleles, given that no significant interaction between rs3087456 and SE alleles was observed. Since a biological link between products of these genes is evident, the genetic contribution from CIITA and class II antigens in the autoimmune process may involve additional unidentified factors.     

Accumulation of polyunsaturated fatty acids by cladocerans: effects of taxonomy,temperature and food

1. Zooplankton are important in transferring dietary nutrients, including polyunsaturated fatty acids (PUFA), up through aquatic food webs. 2. We tested the hypothesis that the taxonomic composition of zooplankton affects the retention and subsequent transfer of PUFA from upwards through the food web. Using laboratory experiments, we investigated dietary PUFA accumulation and bioconversion capacities of six cladoceran species (Ceriodaphnia sp., Daphnia longispina, Daphnia magna, Daphnia pulex, Scapholeberis mucronata and Simocephalus vetulus) fed on two diets (Scenedesmus obliquus and Cryptomonas sp.) that differed in their PUFA profiles. We performed experiments at two different temperatures (14 and 20 °C) to assess the role of temperature in the trophic transfer of PUFA. 3. There was little variation in the concentrations of PUFA in these cladocerans which were controlled by dietary PUFA supply. Moreover, as expected, the concentrations of PUFA in all cladoceran species were higher at low temperature. 4. However, even if the composition of PUFA in the cladoceran species generally corresponded to that in their diet, preferential accumulation of some PUFA was recorded in all these taxa. When fed on a highly unsaturated fatty acid‐deficient diet, all the cladocerans showed some ability to convert C18‐PUFA into arachidonic acid and eicosapentaenoic acid. Interspecific variation in the ability to accumulate and bioconvert PUFA in cladocerans was more pronounced at low temperature (14 °C) for both diets. 5. Our results strongly suggest that in heterogeneous habitats with food partitioning between co‐existing cladocerans, foraging behaviour may affect the transfer of PUFA more strongly than interspecific variation in accumulating and/or bioconverting dietary PUFA.     

Induction of long-term B-cell depletion in refractory rheumatoid arthritis patients preferentially affects autoreactive more than protective humoral immunity

Introduction

B-cell depletion has become a common treatment strategy in anti-TNF-refractory rheumatoid arthritis (RA). Although the exact mechanism of how B-cell depletion leads to clinical amelioration in RA remains to be elucidated, repetitive treatment with B-cell-depleting agents leading to long-term B-cell depletion has been reported to be beneficial. The latter has led to the hypothesis that the beneficial effects of B-cell depletion might act through their influence on pathogenic autoreactive plasma cells.

Methods

In this study, we investigated the effects of a fixed retreatment regimen with anti-CD20 mAbs on the humoral (auto)immune system in a cohort of therapy-refractory RA patients.

Results

Fixed retreatment led to long-term B-cell depletion in peripheral blood, bone marrow and, to a lesser extent, synovium. Also, pathologic autoantibody secretion (that is, anticitrullinated peptide antibodies (ACPAs)) was more profoundly affected by long-term depletion than by physiological protective antibody secretion (that is, against measles, mumps and rubella). This was further illustrated by a significantly shorter estimated life span of ACPA-IgG secretion compared to total IgG secretion as well as protective antibody secretion.

Conclusion

By studying plasma cell function during an extensive 2-year period of B-cell depletion, autoantibody secretion was significantly shorter-lived than physiologically protective antibody secretion. This suggests that the longevity of autoreactive plasma cells is different from protective long-lived plasma cells and might indicate a therapeutic window for therapies that target plasma cells.