Ossicular differentiation of airborne and seismic stimuli in the Cape golden mole (Chrysochloris asiatica)

Comparison between the middle ear anatomy of the Cape golden mole (Chrysochloris asiatica), which exhibits a club-shaped malleus head, and the Desert golden mole (Eremitalpa granti), with a ball-shaped malleus head, suggests differences in sensitivity to airborne sound. Scanning laser Doppler vibrometric measurements of the ossicular behavior in response to both vibration and airborne sound were made in C. asiatica. Two distinct vibrational modes were observed. In response to low-frequency vibration (70–200 Hz), the malleus oscillates about the ligament of the short process of the incus, whereas in response to high-frequency airborne sound (1–6 kHz) the ossicular chain rotates about the long axis of malleus. It is proposed that the club-shaped malleus head in C. asiatica constitutes an adaptation towards bimodal hearing—sensitivity to substrate vibrations and airborne sound. Possible functional differences between these two middle ear types are discussed.     

Role of CD25+ dendritic cells in the generation of Th17 autoreactive T cells in autoimmune experimental uveitis

In the current study, we showed that in vivo administration of an anti-CD25 Ab (PC61) decreased the Th17 response in C57BL/6 mice immunized with the uveitogenic peptide interphotoreceptor retinoid-binding protein, while enhancing the autoreactive Th1 response. The depressed Th17 response was closely associated with decreased numbers of a splenic dendritic cell (DC) subset expressing CD11c(+)CD3(-)CD25(+) and decreased expansion of γδ T cells. We demonstrated that ablation of the CD25(+) DC subset accounted for the decreased activation and the expansion of γδ T cells, leading to decreased activation of IL-17(+) interphotoreceptor retinoid-binding protein-specific T cells. Our results show that an enhanced Th17 response in an autoimmune disease is associated with the appearance of a DC subset expressing CD25 and that treatment of mice with anti-CD25 Ab causes functional alterations in a number of immune cell types, namely DCs and γδ T cells, in addition to CD25(+)αβTCR(+) regulatory T cells.     

Stemness in Hydra - a current perspective

Hydra is a classic and simple model for pattern formation and regeneration research. More recently, it has also been promoted as a model to study ancestral stem cell biology. Three independent cell lineages form the body of the polyp and exhibit characteristics of stem cell systems. In order to define differences in stemness between the ectodermal and endodermal epitheliomuscular cell lineages and the interstitial cell lineage, we compare cellular properties and decision making. We argue that these three lineages are expected to show substantial variation in their stemness-related gene regulatory networks. Finally, we discuss Wnt signalling pathways and Myc oncoproteins, which are beginning to offer a perspective on how proliferation and differentiation might be regulated.     

Immunogenicity of a promiscuous T cell epitope peptide based conjugate vaccine against benzo[a]pyrene: redirecting antibodies to the hapten

The prototype polycyclic aromatic hydrocarbon benzo[a]pyrene (B[a]P) is an environmental pollutant and food contaminant of epidemiological importance. To protect against adverse effects of this ubiquitous carcinogen, we developed an immunoprophylactic strategy based on a B[a]P-protein conjugate vaccine to induce B[a]P specific antibodies (Grova et al., Vaccine. 2009;27:4142-51). Here, we investigated in mice the efficacy of B[a]P-peptide conjugates based on promiscuous T cell epitopes (TCE) into further improve this approach. We showed that B[a]P-peptide conjugates induced very different levels of hapten-specific antibodies with variable functional efficacy, depending on the carrier. In some cases peptide carriers induced a more efficient antibody response against B[a]P than tetanus toxoid as a protein carrier, with the capacity to sequester more B[a]P in the blood. Reducing the carrier size to a single TCE can dramatically shift the antibody bias from the carrier to the B[a]P. Conjugates based on the TCE FIGITEL induced the best anti-hapten response and no antibodies against the carrier peptide. Some peptide conjugates increased the selectivity of the antibodies for the activated metabolite 7,8-diol-B[a]P and B[a]P by one or two orders of magnitude. The antibody efficacy was also demonstrated in their ability to sequester B[a]P in the blood and modulate its faecal excretion (15-56%). We further showed that pre-existing immunity to the carrier from which the TCE was derived did not reduce the immunogenicity of the peptide conjugate. In conclusion, we showed that a vaccination against B[a]P using promiscuous TCEs of tetanus toxin as carriers is feasible even in case of a pre-existing immunity to the toxoid and that some TCE epitopes dramatically redirect the antibody response to the hapten. Further studies to demonstrate a long-term protection of an immunoprophylactic immunisation against B[a]P are warranted.     

Vitamin k-antagonists accelerate atherosclerotic calcification and induce a vulnerable plaque phenotype

Background

Vitamin K-antagonists (VKA) are treatment of choice and standard care for patients with venous thrombosis and thromboembolic risk. In experimental animal models as well as humans, VKA have been shown to promote medial elastocalcinosis. As vascular calcification is considered an independent risk factor for plaque instability, we here investigated the effect of VKA on coronary calcification in patients and on calcification of atherosclerotic plaques in the ApoE^−/− model of atherosclerosis.

Methodology/Principal Findings

A total of 266 patients (133 VKA users and 133 gender and Framingham Risk Score matched non-VKA users) underwent 64-slice MDCT to assess the degree of coronary artery disease (CAD). VKA-users developed significantly more calcified coronary plaques as compared to non-VKA users. ApoE^−/− mice (10 weeks) received a Western type diet (WTD) for 12 weeks, after which mice were fed a WTD supplemented with vitamin K₁ (VK₁, 1.5 mg/g) or vitamin K₁ and warfarin (VK₁&W; 1.5 mg/g & 3.0 mg/g) for 1 or 4 weeks, after which mice were sacrificed. Warfarin significantly increased frequency and extent of vascular calcification. Also, plaque calcification comprised microcalcification of the intimal layer. Furthermore, warfarin treatment decreased plaque expression of calcification regulatory protein carboxylated matrix Gla-protein, increased apoptosis and, surprisingly outward plaque remodeling, without affecting overall plaque burden.

Conclusions/Significance

VKA use is associated with coronary artery plaque calcification in patients with suspected CAD and causes changes in plaque morphology with features of plaque vulnerability in ApoE^−/− mice. Our findings underscore the need for alternative anticoagulants that do not interfere with the vitamin K cycle.     

Horizontal Gene Transfer Contributed to the Evolution of Extracellular Surface Structures: The Freshwater Polyp Hydra Is Covered by a Complex Fibrous Cuticle Containing Glycosaminoglycans and Proteins of the PPOD and SWT (Sweet Tooth) Families

The single-cell layered ectoderm of the fresh water polyp Hydra fulfills the function of an epidermis by protecting the animals from the surrounding medium. Its outer surface is covered by a fibrous structure termed the cuticle layer, with similarity to the extracellular surface coats of mammalian epithelia. In this paper we have identified molecular components of the cuticle. We show that its outermost layer contains glycoproteins and glycosaminoglycans and we have identified chondroitin and chondroitin-6-sulfate chains. In a search for proteins that could be involved in organising this structure we found PPOD proteins and several members of a protein family containing only SWT (sweet tooth) domains. Structural analyses indicate that PPODs consist of two tandem β-trefoil domains with similarity to carbohydrate-binding sites found in lectins. Experimental evidence confirmed that PPODs can bind sulfated glycans and are secreted into the cuticle layer from granules localized under the apical surface of the ectodermal epithelial cells. PPODs are taxon-specific proteins which appear to have entered the Hydra genome by horizontal gene transfer from bacteria. Their acquisition at the time Hydra evolved from a marine ancestor may have been critical for the transition to the freshwater environment.     

Community Assembly of Terrestrial Testate Amoebae: How is the Very First Beginning Characterized?

Testate amoebae play an important role at the very first beginning of succession on land. We used litterbags buried into four different soils to study the early colonization (which occurred within less than 55 days) and establishment of testate amoebae. The litterbag cellulose exposed at the youngest mining site poor in nitrogen and phosphorus was colonized firstly in high abundances, whereas the substrate introduced into the reference sites of undisturbed soil was colonized slowly and in low densities. Besides the (expected) small-sized r-strategists (e.g., Euglypha rotunda, Tracheleuglypha dentata, and Trinema lineare), large-sized K-strategists (e.g., Centropyxis spp., Phryganella acropodia) occurred in remarkably high densities on all sites. Species that colonized the cellulose in high densities (e.g., P. acropodia and T. dentata) were found extremely rarely in the adjacent source substrate and vice versa, stressing the importance of the target substrate quality. In the course of the experiment, the influencing environmental factors became more complex, as shown by redundancy analysis (RDA). Concerning the amoebal community, there was a change from variability to stability, as visualized by cluster analysis. Adjacent litterbags within an investigation site revealed amoebal species and abundances with an increasing similarity during exposition time, whereas the litterbags between the four investigation sites were colonized differently. These observations point to a stochastic (variable) beginning of community assembly, changing to a more deterministic (stable) course. No species replacement has been observed, which is an essential part of most successional theories. Thus, the more flexible concept of "community assembly" should be considered instead of "succession" for protozoa. The stochastic beginning of community assembly and the lack of species replacement are explained by a neutral community model.     

Purification of deoxycytidine kinases from two P815 murine neoplasms and their separation from deoxyguanosine kinase

Deoxycytidine kinase, which catalyzes the phosphorylation of deoxycytidine and 1-βd-arabinofuranosylcytosine (Ara-C) at the 5′-position, has been extracted and extensively purified from a murine neoplasm P815, either sensitive (P815) or resistant (P815/ Ara-C) to 1-β-d-arabinofuranosylcytosine. Gel filtration and ion-exchange chromatography were used to accomplish the purification. The purified enzyme exhibited a single band upon disc electrophoresis. During the extraction procedure an enzyme catalyzing the phosphorylation of deoxyguanosine and deoxyadenosine was successfully separated for the first time from deoxycytidine kinase. The K_m values and turnover numbers with deoxycytidine as phosphate acceptor for the kinase from P815 cells sensitive to 1-β-darabinofuranosylcytosine and that from P815 cells resistant to the drug are 9.3 μm, 4.7 × 10⁶/min and 15.4 μm, 8.0 × 10⁴/min, respectively.