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Ticks are blood feeding arachnids that characteristically take a long blood meal. They must therefore counteract host defence mechanisms such as hemostasis, inflammation and the immune response. This is achieved by expressing batteries of salivary proteins coded by multigene families. We report the in-depth analysis of a tick multigene family and describe five new anticomplement proteins in Ixodes ricinus. Compared to previously described Ixodes anticomplement proteins, these segregated into a new phylogenetic group or subfamily. These proteins have a novel action mechanism as they specifically bind to properdin, leading to the inhibition of C3 convertase and the alternative complement pathway. An excess of non-synonymous over synonymous changes indicated that coding sequences had undergone diversifying selection. Diversification was not associated with structural, biochemical or functional diversity, adaptation to host species or stage specificity but rather to differences in antigenicity. Anticomplement proteins from I. ricinus are the first inhibitors that specifically target a positive regulator of complement, properdin. They may provide new tools for the investigation of role of properdin in physiological and pathophysiological mechanisms. They may also be useful in disorders affecting the alternative complement pathway. Looking for and detecting the different selection pressures involved will help in understanding the evolution of multigene families and hematophagy in arthropods.

To reduce the embryonic pathogenicity of Newcastle disease virus (NDV), escape mutants of the La Sota strain were produced with selected monoclonal antibodies. Immunoselection resulted in the elimination of an epitope by single amino acid substitution (F and HN molecule) or in a conformational change (HN molecule). The embryonic pathogenicity of these escape mutants was reduced and their dose was optimised for in ovo vaccination. Because antibody responses and protection of in ovo vaccinated chicks were similar to controls vaccinated at hatch with the La Sota strain, immunoselection appears a valuable technique to produce attenuated NDV strains, which are candidate in ovo vaccines.

ATP-dependent protease complexes are present in all three kingdoms of life, where they rid the cell of misfolded or damaged proteins and control the level of certain regulatory proteins. They include the proteasome in Eukaryotes, Archea, and Actinomycetales and the HslVU (ClpQY) complex in other eubacteria. We showed that genes homologous to eubacterial HslV (ClpQ) and HslU (ClpY) are present in the genome of trypanosomatid protozoa and are expressed. The features of the cDNAs indicated that bona fide trypanosomatid messengers had been cloned and ruled out bacterial contamination as the source of the material. The N-terminal microsequence of HslV from Leishmania infantum (Protozoa: Kinetoplastida) permitted the identification of the propeptide cleavage site and indicated that an active protease is present. High similarities (≥57.5%) with the prototypical HslV and HslU from Escherichia coli and conservation of residues essential for biochemical activity suggested that a functional HslVU complex is present in trypanosomatid protozoa. The structure of the N-termini of HslV and HslU further suggested mitochondrial localization. Phylogenetic analysis indicated that HslV and HslU from trypanosomatids clustered with eubacterial homologs but did not point to any particular bacterial lineage. Because typical eukaryotic 20S proteasomes are present in trypanosomatids, we concluded that the eubacterial HslVU and the eukaryotic multicatalytic protease are simultaneously present in these organisms. To our knowledge this is the first report of a eubacterial HslVU complex in eukaryotes and, consequently, of the simultaneous occurrence of both a proteasome and HslVU in living cells.

There is an urgent need to develop new therapeutic approaches for the treatment of severe neurological trauma, such as stroke and spinal cord injuries. However, many drugs with potential neuropharmacological activity, such as adenosine, are inefficient upon systemic administration because of their fast metabolization and rapid clearance from the bloodstream. Here, we show that conjugation of adenosine to the lipid squalene and the subsequent formation of nanoassemblies allows prolonged circulation of this nucleoside, providing neuroprotection in mouse stroke and rat spinal cord injury models. The animals receiving systemic administration of squalenoyl adenosine nanoassemblies showed a significant improvement of their neurologic deficit score in the case of cerebral ischaemia, and an early motor recovery of the hindlimbs in the case of spinal cord injury. Moreover, in vitro and in vivo studies demonstrated that the nanoassemblies were able to extend adenosine circulation and its interaction with the neurovascular unit. This Article shows, for the first time, that a hydrophilic and rapidly metabolized molecule such as adenosine may become pharmacologically efficient owing to a single conjugation with the lipid squalene. The systemic circulation time of adenosine is prolonged by forming nanoassemblies with squalene, and this can improve neurologic recovery in mice affected by a stroke or spinal cord injury.

Anorectal melanoma is a rare disorder. There have only been a few cases reported and there is no consensus of treatment. We report a case of 50-year-old Caucasian man presenting intermittent prolapse of an anorectal mass during 6 months with occasional bleeding. Biopsies came up with the diagnosis of malignant melanoma. No distant metastases were found. He underwent an abdominoperineal resection due to internal sphincter invasion. A second tumour was diagnosed in final histologic examination: a dysplastic rectal polyp invaded by the melanoma (collision tumour). At 12 months of follow up he presented loco-regional recurrence (a single pelvic lymph node) and hepatic metastases. He was included in a study protocol comparing new medical treatments (nivolumab versus ipilimumab or both).

Anti-tick vaccination could be an ideal solution to prevent pathogen transmission, but none is currently available against Ixodes ticks. Recently, we showed that adult Ixodes ricinus infestation on mice decreases the specific antibody production to BSA injected during infestation. Here, a kinetic study of seric levels of BSA-specific antibodies was performed to evaluate the B memory cell differentiation in Balb/c mice and the capacity of specific B memory cells to respond to BSA during infestation. We concluded that the tick blood meal inhibits or impairs the local differentiation of mature B cells into plasma cells, but does not alter the formation of memory B cell. Accordingly, this mechanism should not be an impediment to anti-Ixodes vaccination.

Nature Nanotechnology 9, 1054–1062 (2014); published online 24 November 2014; corrected after print 3 December 2014. In the version of this Article originally published, the affiliations of Hakan Eroglu, Omer Faruk Turkoglu, Seçil Caban, Oya Tagit, Niko Hildebrandt and Yilmaz Capan were incorrect; they should have appeared as shown below.

Polyalkylcyanoacrylate (PACA) nanoparticles loaded with doxorubicin allowed multidrug resistance to be overcome in vitro. However, increased cytotoxicity is not always correlated with an increased level of intracellular drug. Although we have previously shown that PACA nanoparticles are not endocytosed by tumour cells, we report here that a direct interaction between nanoparticles and cells is a necessary requirement for overcoming resistance. In addition, the results showed that the degradation products of PACA (mainly polycyanoacrylic acid) in the presence of doxorubicin are able to increase both accumulation and cytotoxicity, thus suggesting the formation of a doxorubicin-polycyanoacrylic acid ion pair. It is therefore concluded that resistance is overcome as a result of both the adsorption of nanoparticles to the cell surface and increased doxorubicin diffusion by the accumulation of an ion pair at the plasma membrane.

The patient was finally provided with medical care at home. Because of the vomiting and the patient's refusal to have a naso-gastric tube, she was rehydrated intravenously with a fluid containing glucose but not enriched with vitamins. [4] showed that on average Wernicke's encephalopathy occurred after 7 weeks of vomiting and in around the 14th week of pregnancy. [...]pregnancy is a high-risk period for thiamine deficiency because of the hypermetabolism induced by the pregnancy and because of the risk of vomiting and digestive disturbances that may increase vitamin losses and reduce intake.