The determinants of land snail diversity along a tropical elevational gradient: insularity,geometry and niches

Aim We investigated the patterns of species richness in land snails and slugs along a tropical elevational gradient and whether these patterns correlate with area, elevation, geographic constraints, and productivity. We did so both at the scale at which land snail population processes take place and at the coarser scale of elevational zones. Location Mount Kinabalu (4096 m) and the adjacent Mount Tambuyukon (2588 m) in Kinabalu Park, Sabah, Malaysian Borneo. Methods We used an effort‐controlled sampling protocol to determine land snail and slug species richness in 142 plots of 0.04 ha at elevations ranging from 570 to 4096 m. Extents of elevational ranges were determined by interpolation, extended where appropriate at the lower end with data from lowlands outside the study area. We used regression analysis to study the relationships between species density and richness on the one hand and elevation and area on the other. This was done for point data as well as for data combined into 300‐m elevational intervals. Results Species density (based on the individual samples) showed a decline with elevation. Elevational range length profiles revealed that range lengths are reduced at greater elevations and that a Rapoport effect is absent. Diversity showed a mild mid‐domain effect on Kinabalu, but not on Tambuyukon. When the data were combined into 300‐m elevational intervals, richness correlated more strongly with elevation than with area. Ecomorphospace was seen to shrink with increasing elevation. Main conclusions The elevational species richness patterns show the combined effects of (1) reduced niche diversity at elevations with lower productivity and (2) historical events in which the upward migration of lowland species as well as the speciation of highland endemics took place.     

Impaired survival of regulatory T cells in pulmonary sarcoidosis

Background

Impaired regulatory T cell (Treg) function is thought to contribute to ongoing inflammatory responses in sarcoidosis, but underlying mechanisms remain unclear. Moreover, it is not known if increased apoptotic susceptibility of Tregs may contribute to an impaired immunosuppressive function in sarcoidosis. Therefore, the aim of this study is to analyze proportions, phenotype, survival, and apoptotic susceptibility of Tregs in sarcoidosis.

Methods

Patients with pulmonary sarcoidosis (n = 58) were included at time of diagnosis. Tregs were analyzed in broncho-alveolar lavage fluid and peripheral blood of patients and healthy controls (HC).

Results

In sarcoidosis patients no evidence was found for a relative deficit of Tregs, neither locally nor systemically. Rather, increased proportions of circulating Tregs were observed, most prominently in patients developing chronic disease. Sarcoidosis circulating Tregs displayed adequate expression of FoxP3, CD25 and CTLA4. Remarkably, in sarcoidosis enhanced CD95 expression on circulating activated CD45RO⁺ Tregs was observed compared with HC, and proportions of these cells were significantly increased. Specifically sarcoidosis Tregs - but not Th cells - showed impaired survival compared with HC. Finally, CD95L-mediated apoptosis was enhanced in sarcoidosis Tregs.

Conclusion

In untreated patients with active pulmonary sarcoidosis, Tregs show impaired survival and enhanced apoptotic susceptibility towards CD95L. Increased apoptosis likely contributes to the insufficient immunosuppressive function of sarcoidosis Tregs. Further research into this field will help determine whether improvement of Treg survival holds a promising new therapeutic approach for chronic sarcoidosis patients.

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-015-0265-8) contains supplementary material, which is available to authorized users.     

Effect of Anti-ApoA-I Antibody-Coating of Stents on Neointima Formation in a Rabbit Balloon-Injury Model

Background and Aims

Since high-density lipoprotein (HDL) has pro-endothelial and anti-thrombotic effects, a HDL recruiting stent may prevent restenosis. In the present study we address the functional characteristics of an apolipoprotein A-I (ApoA-I) antibody coating in vitro. Subsequently, we tested its biological performance applied on stents in vivo in rabbits.

Materials and Methods

The impact of anti ApoA-I- versus apoB-antibody coated stainless steel discs were evaluated in vitro for endothelial cell adhesion, thrombin generation and platelet adhesion. In vivo, response to injury in the iliac artery of New Zealand white rabbits was used as read out comparing apoA-I-coated versus bare metal stents.

Results

ApoA-I antibody coated metal discs showed increased endothelial cell adhesion and proliferation and decreased thrombin generation and platelet adhesion, compared to control discs. In vivo, no difference was observed between ApoA-I and BMS stents in lumen stenosis (23.3±13.8% versus 23.3±11.3%, p=0.77) or intima surface area (0.81±0.62 mm² vs 0.84±0.55 mm², p=0.85). Immunohistochemistry also revealed no differences in cell proliferation, fibrin deposition, inflammation and endothelialization.

Conclusion

ApoA-I antibody coating has potent pro-endothelial and anti-thrombotic effects in vitro, but failed to enhance stent performance in a balloon injury rabbit model in vivo.     

Thermal Unfolding of a Mammalian Pentameric Ligand-gated Ion Channel Proceeds at Consecutive,Distinct Steps

Pentameric ligand-gated ion channels (LGICs) play an important role in fast synaptic signal transduction. Binding of agonists to the β-sheet-structured extracellular domain opens an ion channel in the transmembrane α-helical region of the LGIC. How the structurally distinct and distant domains are functionally coupled for such central transmembrane signaling processes remains an open question. To obtain detailed information about the stability of and the coupling between these different functional domains, we analyzed the thermal unfolding of a homopentameric LGIC, the 5-hydroxytryptamine receptor (ligand binding, secondary structure, accessibility of Trp and Cys residues, and aggregation), in plasma membranes as well as during detergent extraction, purification, and reconstitution into artificial lipid bilayers. We found a large loss in thermostability correlating with the loss of the lipid bilayer during membrane solubilization and purification. Thermal unfolding of the 5-hydroxytryptamine receptor occurred in consecutive steps at distinct protein locations. A loss of ligand binding was detected first, followed by formation of different transient low oligomeric states of receptor pentamers, followed by partial unfolding of helical parts of the protein, which finally lead to the formation receptor aggregates. Structural destabilization of the receptor in detergents could be partially reversed by reconstituting the receptor into lipid bilayers. Our results are important because they quantify the stability of LGICs during detergent extraction and purification and can be used to create stabilized receptor proteins for structural and functional studies.     

Host cell responses of Salmonella typhimurium infected human dendritic cells

Live attenuated Salmonella are attractive vaccine candidates for mucosal application because they induce both mucosal immune responses and systematic immune responses. After breaking the epithelium barrier, Salmonella typhimurium is found within dendritic cells (DC) in the Peyer's patches. Although there are abundant data on the interaction of S. typhimurium with murine epithelial cells, macrophages and DC, little is known about its interaction with human DC. Live attenuated S. typhimurium have recently been shown to efficiently infect human DC in vitro and induce production of cytokines. In this study, we have analysed the morphological consequences of infection of human DC by the attenuated S. typhimurium mutant strains designated PhoPc, AroA and SipB and the wild-type strains of the American Type Culture Collection (Manassas, VA, USA), ATCC 14028 and ATCC C53, by electron microscopy at 30 min, 3 h and 24 h after exposure. Our results show that genetic background of the strains profoundly influence DC morphology following infection. The changes included (i) membrane ruffling; (ii) formation of tight or spacious phagosomes; (iii) apoptosis; and (iv) spherical, pedunculated membrane-bound microvesicles that project from the plasma membrane. Despite the fact that membrane ruffling was much more pronounced with the two virulent strains, all mutants were taken up by the DC. The microvesicles were induced by all the attenuated strains, including SipB, which did not induce apoptosis in the host cell. These results suggest that Salmonella is internalized by human DC, inducing morphological changes in the DC that could explain immunogenicity of the attenuated strains.     

What do we need to know about speciation?

Speciation has been a major focus of evolutionary biology research in recent years, with many important advances. However, some of the traditional organising principles of the subject area no longer provide a satisfactory framework, such as the classification of speciation mechanisms by geographical context into allopatric, parapatric and sympatry classes. Therefore, we have asked where speciation research should be directed in the coming years. Here, we present a distillation of questions about the mechanisms of speciation, the genetic basis of speciation and the relationship between speciation and diversity. Our list of topics is not exhaustive; rather we aim to promote discussion on research priorities and on the common themes that underlie disparate speciation processes.     

CRIg: a macrophage complement receptor required for phagocytosis of circulating pathogens

The complement system serves an important role in clearance of pathogens, immune complexes, and apoptotic cells present in the circulation. Complement fragments deposited on the particle surface serve as targets for complement receptors present on phagocytic cells. Although Kupffer cells, the liver resident macrophages, play a dominant role in clearing particles in circulation, complement receptors involved in this process have yet to be identified. Here we report the identification and characterization of a Complement Receptor of the Immunoglobulin superfamily, CRIg, that binds complement fragments C3b and iC3b. CRIg expression on Kupffer cells is required for efficient binding and phagocytosis of complement C3-opsonized particles. In turn, Kupffer cells from CRIg-deficient mice are unable to efficiently clear C3-opsonized pathogens in the circulation, resulting in increased infection and mortality of the host. CRIg therefore represents a dominant component of the phagocytic system responsible for rapid clearance of C3-opsonized particles from the circulation.     

Radio-opaque and surface-functionalized polymer microparticles: potentially safer biomaterials for different injection therapies

Injectable polymer particles with a diameter in the range of 30-300 microm find applications as a biomaterial in different clinical fields, such as cosmetic surgery, reconstructive surgery, and urology. However, clinical effects tend to disappear after several months, either due to migration of the particles away from the injection site (caused by weak adherence with the surrounding soft tissues) or due to fibrosis (caused by excessive encapsulation of the particles by fibrous tissue). Little is known about the fate of injected microparticles, due to the fact that they are extremely difficult to trace in a noninvasive manner. Design, synthesis, and characterization of new polymeric microspheres with two additional features that can enhance safety and can help to overcome drawbacks of existing products are reported. First, the new microparticles feature clear radio-opacity (X-ray visibility) as they are prepared on the basis of a reactive methacrylic monomer that contains covalently bound iodine. Model experiments reveal that the level of X-ray contrast is sufficient for clinical monitoring; they can be visualized both during the injection and afterward. The particles feature excellent cytocompatibility in vitro and in vivo. Second, a method is explored to functionalize the surface of the particles, for example, through immobilization of collagen. Other extracellular matrix proteins can also be immobilized, and this provides a mechanism to control anchoring of the particles in soft tissue. The results are briefly discussed in the context of improved biomaterials, contemporary X-ray imaging, and control over biomaterial-soft tissue interactions in vivo.