Persistent joint swelling and Borrelia-specific antibodies in Borrelia garinii-infected mice after eradication of vegetative spirochetes with antibiotic treatment

We wanted to study the pathogenesis and the long-term manifestations of Borrelia garinii infection in SJL and C3H/He mice. We report here that B. garinii A218 causes a persisting infection in these mouse strains. Mice infected with intracutaneous inoculation of B. garinii at 4-5 weeks of age developed a disseminated infection and joint swelling within 2 weeks of inoculation and remained infected with joint symptoms until the end of follow-ups of up to 52 weeks. Treatment with ceftriaxone or ampicillin at 18 or 44 weeks of infection did not affect the joint swelling during the follow-ups of 19 and 8 weeks, respectively. However, B. garinii could not be cultured from any of the post mortem tissue samples of the treated mice, whereas the spirochete grew from samples of all untreated infected animals. Borrelia-specific IgG antibodies were detectable after 2 weeks of infection, and in late infection, all mice had high anti-borrelia IgG levels. Antibiotic treatment had no effect on antibody levels. Histology showed only slight changes in the joints of the infected mice with occasional lymphocyte infiltration, synovial proliferation and slight involvement of the Achilles' tendon. No difference was seen in the findings between ceftriaxone-treated and untreated mice. The results suggest that the presence of vegetative spirochetes is no prerequisite for persisting joint symptoms and elevated anti-borrelia IgG levels in these B. garinii-infected mice.     

The interferon-inducible RNA helicase, mda-5, is involved in measles virus-induced expression of antiviral cytokines

Activation of host cell antiviral responses is mediated by receptors detecting the presence of viruses. Here we have studied the role of double-stranded RNA (dsRNA) binding molecules melanoma differentiation-associated gene 5 (mda-5), retinoic acid inducible gene I (RIG-I), and Toll-like receptor 3 (TLR3) in measles virus (MV)-induced expression of antiviral cytokines and chemokines in human A549 lung epithelial cells and human umbilical vein endothelial cells (HUVECs). We show that MV infection results in the activation of mda-5, RIG-I, and TLR3 gene expression that is followed by high expression of interferon (IFN)-beta, interleukin (IL)-28 and IL-29, CCL5, and CXCL10 genes. We also demonstrate that IFN-alpha and IFN-beta upregulate mda-5, RIG-I, and TLR3 gene expression in epithelial and endothelial cell lines. Forced expression of mda-5, but not that of RIG-I or TLR3, leads to enhanced IFN-beta promoter activity in MV-infected A549 cells. Our results suggest that IFN-inducible mda-5 is involved in MV-induced expression of antiviral cytokines.     

Discovery, SAR, and X-ray structure of novel biaryl-based dipeptidyl peptidase IV inhibitors

The discovery, SAR, and X-ray crystal structure of novel biarylaminoacyl-(S)-2-cyano-pyrrolidines and biarylaminoacylthiazolidines as potent inhibitors of dipeptidyl peptidase IV (DPP IV) are reported.     

Attempt to treat congenital pseudarthrosis of the tibia with mesenchymal stromal cell transplantation

Background aimsCongenital pseudarthrosis of the tibia (CPT) caused by neurofibromatosis type 1 (NF1) is a refractory disease occurring in childhood. We present two cases that had failed all earlier treatment attempts and, as a last treatment attempt, the patients were chosen to receive mesenchymal stromal cell (MSC) transplantation prior to amputation.MethodsThe MSC from bone marrow (BM) were harvested from the iliac crest and cultured in osteoinductive medium for 3 weeks. The cultured MSC were injected in solution into BM canals of the tibia and around the resection line or bone defect in a 3-dimensional collagen sponge scaffold. After the MSC transplantation, the patients were monitored during a 10-month follow-up period. In both cases, bone formation at the pseudarthrosis site was observed and two of three treated bone defects healed. For clinical reasons not related to cell transplantation, such as new infection and pseudarthrosis and severe shortening of the leg, both extremities were finally amputated and bone samples were analyzed to evaluate MSC therapy effect and safety.ResultsMSC transplantation normalized bone remodeling, promoted bone resorption and improved the overall structure of bone. The number of osteoclasts in the cortical bone was 2-fold higher compared with the monitored situation before MSC transfer. In addition, the mineral content of the bone improved after transplantation. We could see no sign of aberrant bone formation or malignant transformation.ConclusionsOur data suggest that MSC transplantation is a possibility for treatment of CPT caused by NF1 in less severe cases without adjunct defects.     

Synthesis of novel quaternary chitosan derivatives via N-Chloroacyl-6-O-triphenylmethylchitosans

Various quaternary chitosan derivative structures were synthesized by reacting N-chloroacyl-6-O-triphenylmethylchitosans with tertiary amines. Full substitutions were obtained from the quaternization reactions and the obtained water-soluble quaternary chitosan derivatives were thoroughly characterized with (1)H NMR, (13)C NMR, (1)H-(13)C HSQC NMR, and FT-IR.     

Impact of crop species on bacterial community structure during anaerobic co-digestion of crops and cow manure

The bacterial communities in three continuously stirred tank reactors co-digesting cow manure with grass silage, oat straw, and sugar beet tops, respectively, were investigated by 16S rRNA gene-based fingerprints and clone libraries. The analyses revealed both clearly distinct and similar phylotypes in the bacterial communities between the reactors. The major groups represented in the three reactors were Clostridia, unclassified Bacteria, and Bacteroidetes. Phylotypes affiliated with Bacilli or Deltaproteobacteria were unique to the sugar beet and straw reactor, respectively. Unclassified Bacteria dominated in sugar beet reactor while in the straw and grass reactor Clostridia was the dominant group. An increase in organic loading rate from 2 to 3 kg volatile solids m^?3 d^?1 resulted in larger changes in the bacterial community in the straw compared to grass reactor. The study shed more light on the evolution of bacterial community during anaerobic co-digestion of different crops and manure to methane.     

Signals of major histocompatibility complex overdominance in a wild salmonid population

The major histocompatibility complex (MHC) contains the most variable genes in vertebrates, but despite extensive research, the mechanisms maintaining this polymorphism are still unresolved. One hypothesis is that MHC polymorphism is a result of balancing selection operating by overdominance, but convincing evidence for overdominant selection in natural populations has been lacking. We present strong evidence consistent with MHC-specific overdominance in a free-living population of Arctic charr (Salvelinus alpinus) in northernmost Europe. In this population, where just two MHC alleles were observed, MHC heterozygous fish had a lower parasite load, were in better condition (as estimated by a fatness indicator) and had higher survival under stress than either of the homozygotes. Conversely, there was no consistent association between these fitness measures and assumedly neutral microsatellite variability, indicating an MHC-specific effect. Our results provide convincing empirical evidence consistent with the notion that overdominance can be an important evolutionary mechanism contributing to MHC polymorphism in wild animal populations. They also support a recent simulation study indicating that the number of alleles expected to be maintained at an MHC loci can be low, even under strong heterozygote advantage.     

Rewetting of Cutaway Peatlands: Are We Re‐Creating Hot Spots of Methane Emissions?

Hot spots of CH₄ emissions are a typical feature of pristine peatlands at the microsite and landscape scale. To determine whether rewetting and lake construction in a cutaway peatland would result in the re‐creation of hot spots, we first measured CH₄ fluxes over a 2‐year period with static chambers and estimated annual emissions. Second, to assess whether rewetting and lake creation would produce hot spots at the landscape level, we hypothesized a number of alternative land use scenarios for the peatland following the cessation of peat extraction. Using the results from this study and other studies from literature, we calculated the global warming potential (GWP) of each scenario and the respective contribution of CH₄. The results showed that hot spots of CH₄ fluxes were observed as a consequence of microsite‐specific differences in water table (WT) position and plant productivity. CH₄ fluxes were closely related to peat temperature at 10 cm depth and WT position. Annual emissions ranged from 4.3 to 38.8 g CH₄ m^?2 yr^?1 in 2002 and 3.2 to 28.8 g CH₄ m^?2 yr^?1 in 2003. The scenario results suggest that lake creation is likely to result in the re‐creation of a hot spot at the landscape level. However, the transition from cutaway to wetland ecosystem may lead to a reduction in the GWP of the peatland.