Host striatal projections into fetal ventral mesencephalic tissue grafted to the striatum of immature or adult rat

We have previously reported that few striatal axons from adult host brain innervate intrastriatal grafts of fetal ventral mesencephalic tissue. To see whether the immature rat brain would favor striatal innervation of the graft, unilateral implantation of fetal ventral mesencephalic tissue was carried out at 7 (P7), 14 (P14), or 60 (adults) days of age in neonatally dopamine- (DA)-lesioned and nonlesioned rats. Immunocytochemistry for tyrosine hydroxylase (TH), and/or dopamine- and adenosine 3′,5′-monophosphate-regulated phosphoprotein-32 (DARPP-32) was performed 2–6 months later. In the great majority of immature and in all adult recipients, the resulting graft consisted of a distinct intrastriatal mass of tissue surrounded by the host parenchyma. Most TH-immunopositive neurons were found within the confines of such grafts, although some were lying at short distances into the host striatal tissue, particularly in immature recipients. In a few immature recipients, there was, however, extensive intermingling of TH-positive neurons with the adjacent host brain tissue. In all recipients grafted at P7, P14, or as adults, the distinct, intra-parenchymal grafts contained moderate numbers of DARPP-32-positive processes, mainly at their periphery. These results indicate that the limited capacity of host striatal neurons to grow axons into transplanted fetal ventral mesencephalic tissue is not markedly different in young versus adult rats. A better integration of the ventral mesencephalic graft into the striatal circuitry of immature — as opposed to adult — recipients should therefore rely more on the higher tendency of DA neurons to become located into the host tissue following transplantation in young rats.     

Crystal structure and functional mapping of human ASMT,the last enzyme of the melatonin synthesis pathway

Abstract: Melatonin is a synchronizer of many physiological processes. Abnormal melatonin signaling is associated with human disorders related to sleep, metabolism, and neurodevelopment. Here, we present the X‐ray crystal structure of human N‐acetyl serotonin methyltransferase (ASMT), the last enzyme of the melatonin biosynthesis pathway. The polypeptide chain of ASMT consists of a C‐terminal domain, which is typical of other SAM‐dependent O‐methyltransferases, and an N‐terminal domain, which intertwines several helices with another monomer to form the physiologically active dimer. Using radioenzymology, we analyzed 20 nonsynonymous variants identified through the 1000 genomes project and in patients with neuropsychiatric disorders. We found that the majority of these mutations reduced or abolished ASMT activity including one relatively frequent polymorphism in the Han Chinese population (N17K, rs17149149). Overall, we estimate that the allelic frequency of ASMT deleterious mutations ranges from 0.66% in Europe to 2.97% in Asia. Mapping of the variants on to the 3‐dimensional structure clarifies why some are harmful and provides a structural basis for understanding melatonin deficiency in humans.     

Dorsal costo-vertebral joint as a rare localization of Staphylococcus aureus sepsis

Background

Septic arthritis of the costovertebral thoracic joint is a rare site infection. We report an isolated case of septic arthritis of the 10th costo-vertebral right joint with osteitis due to Staphylococcus aureus.

Ru(ii)–N-heterocyclic carbene complexes: synthesis,characterization, transfer hydrogenation reactions and biological determination

A series of ruthenium(ii) complexes with N-heterocyclic carbene ligands were successfully synthesized by transmetalation reactions between silver(i) N-heterocyclic carbene complexes and [RuCl₂(p-cymene)]₂ in dichloromethane under Ar conditions. All new compounds were characterized by spectroscopic and analytical methods. These ruthenium(ii)–NHC complexes were found to be efficient precatalysts for the transfer hydrogenation of ketones by using 2-propanol as the hydrogen source in the presence of KOH as a co-catalyst. The antibacterial activity of ruthenium N-heterocyclic carbene complexes 3a–f was measured by disc diffusion method against Gram positive and Gram-negative bacteria. Compounds 3d exhibited potential antibacterial activity against five bacterial species among the six used as indicator cells. The product 3e inhibits the growth of all the six tested microorganisms. Moreover, the antioxidant activity determination of these complexes 3a–f, using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azinobis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS) as reagent, showed that compounds 3b and 3d possess DPPH and ABTS antiradical activities. From a concentration of 1 mg ml⁻¹, these two complexes presented a similar scavenging activity to that of the two used controls gallic acid (GA) and butylated hydroxytoluene (BHT). From a concentration of 10 mg ml⁻¹, the percentage inhibition of complexes 3b and 3d was respectively 70% and 90%. In addition, these two Ru–NHC complexes exhibited antifungal activity against Candida albicans. Investigation of the anti-acetylcholinesterase activity of the studied complexes showed that compounds 3a, 3b, 3d and 3e exhibited good activity at 100 μg ml⁻¹ and product 3d is the most active. In a cytotoxicity study the complexes 3 were evaluated against two human cancer cell lines MDA-MB-231 and MCF-7. Both 3d and 3e complexes were found to be active against the tested cell lines showing comparable activity with examples in the literature.

A series of ruthenium(ii) complexes with N-heterocyclic carbene ligands were successfully synthesized by transmetalation reactions between silver(i) N-heterocyclic carbene complexes and [RuCl₂(p-cymene)]₂ in dichloromethane under Ar conditions.     

Association study of human leukocyte antigen-DRB1 alleles with rheumatoid arthritis in south Tunisian patients

The aim of this study is to explore relationship between HLA-DRB1 alleles and the susceptibility and clinical features of rheumatoid arthritis (RA) in the south Tunisian population. We studied 142 RA patients and 123 controls matched for age, sex, and ethnicity. HLA-DRB1 genotyping and HLA-DRB1*04 subtypes were performed using polymerase chain reaction/sequence-specific primers. Association was assessed based on the χ (2) test and odds ratio with 95% confidence interval. For multiple comparisons, p value was corrected (p (c)) with Bonferroni test. Two alleles, HLA-DRB1*04 (p=0.045, p(c)=NS) and HLA-DRB1*10 (p=0.021, p(c)=NS), were found to have increased frequencies in RA patients compared to controls. In contrast HLA-DRB1*08 allele was found to have a decreased frequency in patients compared to controls (p=0.044, p(c)=NS). Molecular subtyping of the most prevalent allele (DRB1*04) revealed increased frequencies of HLA-DRB1*04:05 in patients compared to controls (p=0.013, p(c)=NS) whereas HLA-DRB1*04:02 showed a protective effect (p=0.005, p(c)=0.04). Moreover, stratified analyses indicated statistically significant associations between HLA-DRB1*04 allele and anti-cyclic peptides antibodies positivity (ACPA(+)) and rheumatoid factor positivity (RF(+); p(c)=0.03, for both subgroups), HLA-DRBI*10 and ACPA(+) and the presence of another autoimmune disease (p(c)=0.05 and p(c)=0.007, respectively), and HLA-DRB1*04:05 and RF(+) and erosion (p(c)=0.005 and p(c)=0.049; respectively). A significant decrease in the frequency of the DRB1*04:02 allele was observed in patients with ACPA(+) and RF(+) subgroups (p(c)=0.04 and p(c)=0.02, respectively). Our results showed that there was a trend of positive association of HLA-DRB1*04 and HLA-DRB1*10 with RA as such and significant associations with the disease severity in the south Tunisian population.