Anti-CD154 mAb and Rapamycin Induce T Regulatory Cell Mediated Tolerance in Rat-to-Mouse Islet Transplantation

Background

Anti-CD154 (MR1) monoclonal antibody (mAb) and rapamycin (RAPA) treatment both improve survival of rat-to-mouse islet xenograft. The present study investigated the effect of combined RAPA/MR1 treatment on rat-to-mouse islet xenograft survival and analyzed the role of CD4⁺CD25⁺Foxp3⁺ T regulatory cells (Treg) in the induction and maintenance of the ensuing tolerance.

Methodology/Principal Findings

C57BL/6 mice were treated with MR1/RAPA and received additional monoclonal anti-IL2 mAb or anti CD25 mAb either early (0–28 d) or late (100–128 d) post-transplantation. Treg were characterised in the blood, spleen, draining lymph nodes and within the graft of tolerant and rejecting mice by flow cytometry and immunohistochemistry. Fourteen days of RAPA/MR1 combination therapy allowed indefinite islet graft survival in >80% of the mice. Additional administration of anti-IL-2 mAb or depleting anti-CD25 mAb at the time of transplantation resulted in rejection (100% and 89% respectively), whereas administration at 100 days post transplantation lead to lower rejection rates (25% and 40% respectively). Tolerant mice showed an increase of Treg within the graft and in draining lymph nodes early post transplantation, whereas 100 days post transplantation no significant increase of Treg was observed. Rejecting mice showed a transient increase of Treg in the xenograft and secondary lymphoid organs, which disappeared within 7 days after rejection.

Conclusions/Significances

These results suggest a critical role for Treg in the induction phase of tolerance early after islet xenotransplantation. These encouraging data support the need of developing further Treg therapy for overcoming the species barrier in xenotransplantation.     

Effect of ammonium ions on spiramycin biosynthesis in Streptomyces ambofaciens

The physiological significance of trans unsaturated fatty acids, which are constituents of membrane lipids of the phenol-degrading bacterium Pseudomonas putita P8, was studied. The addition of phenol or phenol derivatives to the cells induced the formation of trans unsaturated fatty acids, yielding an overall maximal amount of 41.3% of total fatty acids. The inhibition of de-novo lipid synthesis by cerulenin prevented the change in the degree of saturation in the lipids. However, the cells could still respond to phenols with an amplified conversion of cis into trans unsaturated fatty acids, which is apparently a post-synthesis mechanism of isomerization of the double bond. The cis/trans conversion correlated with growth inhibition induced by toxic concentrations of 4-chlorophenol, whereas only growing cells were able to change the degree of saturation. In cells that were protected against phenol by immobilization in calcium alginate, the conversion of cis into trans fatty acids occurred at higher toxin concentrations compared with free cells. Cells entering the stationary growth phase increased the prodortion of saturated to unsaturated fatty acids but maintained a constant trans/cis ratio.P. putida P8 reacted to an increase or decrease in the growth temperature with an appropriate change in the ratio of saturated to unsaturated fatty acids and in cells inhibited by cerulenin with a change in the trans/cis ratio. This study shows that the physiological role of the cis/trans conversion is probably the regulation of membrane fluidity when the most important mechanism for this, the modification of the degree of saturation, cannot by used by the cells due to inhibition of growth and lipid biosynthesis. Correspondence to: H. Keweloh     

Impact of some environmental factors on growth and production of ochratoxin A of/by <Emphasis Type="Italic">Aspergillus tubingensis,A. niger</Emphasis>, and <Emphasis Type="Italic">A. carbonarius</Emphasis> isolated from moroccan grapes

The effects of temperature, water activity (a_w), incubation time, and their combinations on radial growth and ochratoxin A (OTA) production of/by eight Aspergillus niger aggregate strains (six A. tubingensis and two A. niger) and four A. carbonarius isolated from Moroccan grapes were studied. Optimal conditions for the growth of most studied strains were shown to be at 25°C and 0.95 a_w. No growth was observed at 10°C regardless of the water activity and isolates. The optimal temperature for OTA production was in the range of 25°C∼30°C for A. carbonarius and 30°C∼37°C for A. niger aggregate. The optimal a_w for toxin production was 0.95∼0.99 for A. carbonarius and 0.90∼0.95 for A. niger aggregate. Mean OTA concentration produced by all the isolates of A. niger aggregate tested at all sampling times shows that maximum amount of OTA (0.24 μg/g) was produced at 37°C and 0.90 a_w. However, for A. carbonarius, mean maximum amounts of OTA (0.22 μg/g) were observed at 25°C and 0.99 a_w. Analysis of variance showed that the effects of all single factors (a_w, isolate, temperature and incubation time) and their interactions on growth and OTA production were highly significant.     

The tri–μ–hydrido–bis[(η5–C5Me5)aluminum(III)] theoretical study, the assets of sandwiched M2H3 (M of 13th group elements) stability

The stability of the tri–μ–hydrido–bis[(η⁵–C₅Me₅)aluminum], Cp*₂Al₂H₃, 1 is studied at B3LYP/6–311+G(d,p), CCSD(T)//B3LYP/6–311+G(d,p) and MP4//B3LYP/6–311+G(d,p) levels. The coordination between Al₂H₃ entity and both C₅(CH₃)₅ groups is ensured by strong electrostatic and orbital interactions. The orbital analysis of the interacting fragments shows that Al₂H₃ acceptor, which keeps its tribridged structure, implies the vacant ( \texta₁￠ ) \left( {{\text{a}}_1^\prime } \right) and five antibonding (a₂^￠￠ a_2^{\prime \prime } , e′ and e″) molecular orbitals to interact with two orbitals mixtures, b₁ and e" of the donors (C₅Me₅). When we take into account the solvent effect, the computation shows that 1 seems to be stable in condensed phase with a tribridged bond between the Al atoms [Cp*Al(μ-H)₃AlCp*], whereas in the gas phase, the monobridged Cp*AlH(μ-H)AlHCp* 4 is slightly favored (4 kcal mol⁻¹). We propose that 1 could be prepared thanks to Cp*Al (2) and Cp*AlH₂ (3) reaction in acidic medium. The experimental treatment of this type of metallocenes would contribute to the development of the organometallic chemistry of 13th group elements.      

Environmental and economic issues arising from the pooling of SMEs’ supply chains: case study of the food industry in western France

Supply chains pooling is an emergent strategy for improving logistical performance. The pooling concept consists in transferring the effort of coordination for consolidating independent operators’ flows towards an ad hoc pooled system. This organisation results from a design of a pooled logistics network by merging different supply chains to share transport and logistics resources in order to improve logistics performance. In this case study, the pooling concept is applied to a collection of small and medium-sized western France food suppliers serving the same retail chain. In order to demonstrate the efficiency of the pooling, the existing transport organisation was compared to various pooling scenarios. The methodology consisted in accessing a current situation through a survey of the flow of goods at one of the main distribution centre of the studied supply network, then comparing this situation with three other pooling scenarios. Using supply network optimisation models, these scenarios were assessed considering cost and CO₂ emission levels. This study demonstrates the interest of transport pooling in the case independent shipping networks of Small and Medium Enterprises compared to the partially know existing strategies adopted by logistics service providers for less than truckload shipments. Moreover, it suggests that there is no dominant supply organisation and that transport pooling is a new stimulus for network design. These results also bring new research perspectives for generalisation of pooling and gain sharing within large coalitions.     

Early Triassic Archosaur-Dominated Footprint Assemblage from the Argana Basin (Western High Atlas,Morocco)

An assemblage of abundant and well-preserved tetrapod footprints has been discovered in the Tanamert Member (T3) of the Triassic Timezgadiouine Formation (Argana basin, western High Atlas, Morocco). It is the first fossil record from T3. Surfaces from different localities show a uniform tetrapod ichnofauna that consists of chirotherian and small lacertoid forms. The chirotherians are assigned to the plexus Protochirotherium—Synaptichnium, their trackmakers interpreted as basal archosaurs. The lacertoid imprints show close affinities with Rhynchosauroides and may reflect archosauromorphs or lepidosauromorphs. Protochirotherium—Synaptichnium assemblages are characteristic of the Early Triassic and were known previously only from units of this age in central Europe. Biostratigraphically, the European record implies a wide-spread pre-Anisian Protochirotherium—Synaptichnium dominated assemblage preceding the first appearance of Chirotherium barthii near the Olenekian-Anisian boundary. The stratigraphic position of T3 between Late Permian (uppermost T2) and Middle Triassic (T4) and the European correlatives suggest an Early Triassic age of this unit. It is the first record of Early Triassic continental deposits in Morocco. The surfaces from T3 open up perspectives for further contributions to ecology, biogeography and locomotion of early archosaurs. Furthermore, excellent outcrops and quality of footprint preservation in the Argana basin offer a potential for clarification of ichnotaxonomic and biostratigraphic issues.     

Characterization of two D-beta-hydroxybutyrate dehydrogenase populations in heavy and light mitochondria from jerboa (Jaculus orientalis) liver

Mitochondrial membrane-bound and phospholipid-dependent D-beta-hydroxybutyrate dehydrogenase (BDH) (EC 1.1.1.30), a ketone body converting enzyme in mitochondria, has been studied in two populations of mitochondria (heavy and light) of jerboa (Jaculus orientalis) liver. The results reveal significant differences between the BDH of the two mitochondrial populations in terms of protein expression, kinetic parameters and physico-chemical properties. These results suggest that the beta-hydroxybutyrate dehydrogenases from heavy and light mitochondria are isoform variants. These differences in BDH distribution could be the consequence of cell changes in the lipid composition of the inner mitochondrial membrane of heavy and light mitochondria. These changes could modify both BDH insertion and BDH lipid-dependent catalytic properties.