Evidence for a rapid rate of molecular evolution at the hypervariable and immunogenic Mycobacterium tuberculosis PPE38 gene region

Background  

PPE38 (Rv 2352c) is a member of the large PPE gene family of Mycobacterium tuberculosis and related mycobacteria. The function of PPE proteins is unknown but evidence suggests that many are cell-surface associated and recognised by the host immune system. Previous studies targeting other PPE gene members suggest that some display high levels of polymorphism and it is thought that this might represent a means of providing antigenic variation. We have analysed the genetic variability of the PPE38 genomic region on a cohort of M. tuberculosis clinical isolates representing all of the major phylogenetic lineages, along with the ancestral M. tuberculosis complex (MTBC) member M. canettii, and supplemented this with analysis of publicly available whole genome sequences representing additional M. tuberculosis clinical isolates, other MTBC members and non tuberculous mycobacteria (NTM). Where possible we have extended this analysis to include the adjacent plcABC and PPE39/40 genomic regions.     

Citicoline (CDP-choline): What role in the treatment of complications of infectious diseases

A dysregulated host immune response, as opposed to the intrinsic virulence of a microbial pathogen induces a large part of the pathology seen in infectious diseases. However, current therapies are designed to target the pathogen rather than the underlying pathogenic mechanisms responsible for the manifestation of the pathology. Recent studies have highlighted the role of endothelial cell alteration in the pathology induced in sepsis and cerebral malaria. The endothelial onslaught described, is similar to that seen during ischemia reperfusion in stroke. Protecting endothelial cell membranes during sepsis and cerebral malaria, using citicoline in the same way as in stroke, has thus emerged as a new strategy that needs to be evaluated urgently. Citicoline is a natural compound that is registered for use in ischemic stroke, head trauma and neurological disorders. It enters the phosphatidylcholine synthesis pathway as a rate-limiting step and is involved in the modulation of a large number of metabolic pathways and neurotransmitter levels, and also in the biosynthesis of phospholipids in neuronal membranes. This short review highlights the potential role of citicoline as part of adjunct therapy in the treatment of infectious diseases.     

Differences in δ13C and δ15N stable isotopes in the pearly razorfish Xyrichtys novacula related to the sex,location and spawning period

In the present study, Xyrichtys novacula (Labridae) were sampled at five locations around the islands of Ibiza and Formentera (western Mediterranean Sea). Isotopic signatures of δ¹³C, δ¹⁵N and the C:N ratio were analysed in relation to locality, sex and size differences. δ¹³C and δ¹⁵N partitioning was also studied in the reproductive spawning period. There were significant differences in the δ¹³C signature between localities for both sexes, but not for δ¹⁵N. Sex differences were also found with a mean ±s.e . value of ?17·38 ± 0·06‰δ¹³C and 8·36 ± 0·05‰δ¹⁵N for females and ?17·17 ± 0·07‰δ¹³C and 8·80 ± 0·06‰δ¹⁵N for males. Increasing total length in both sexes was positively correlated with δ¹⁵N enrichment and a significant positive linear regression was established for both variables. During the reproductive spawning period, there were changes in δ¹³C fractioning with enrichment in postspawning females and males (with respect to prespawning and spawning periods) and δ¹⁵N impoverishment in postspawning females (with respect to prespawning and spawning periods). Xyrichtys novacula uses local food sources, as confirmed by δ¹³C and δ¹⁵N, and females and males use different food sources, thus avoiding intraspecific competition. This was confirmed by δ¹⁵N enrichment as size increased. Spawning leads to special requirements for gonad maturation, which is reflected in the isotopic signatures for both sexes.     

The role of human HtrA1 in arthritic disease

Human HtrA1 belongs to a widely conserved family of serine proteases involved in various aspects of protein quality control and cell fate. Although HtrA1 has been implicated in the pathology of several diseases, its precise biological functions remain to be established. Through identification of potential HtrA1 targets, studies presented herein propose that within the context of arthritis pathology HtrA1 contributes to cartilage degradation. Elevated synovial HtrA1 levels were detected in fluids obtained from rheumatoid and osteoarthritis patients, with synovial fibroblasts identified as a major source of secreted HtrA1. Mass spectrometry analysis of potential HtrA1 substrates within synovial fluids identified fibronectin as a candidate target, and treatment of fibronectin with recombinant HtrA1 led to the generation of fibronectin-degradation products that may be involved in cartilage catabolism. Consistently, treatment of synovial fibroblasts with HtrA1 or HtrA1-generated fibronectin fragments resulted in the specific induction of matrix metalloprotease 1 and matrix metalloprotease 3 expression, suggesting that HtrA1 contributes to the destruction of extracellular matrix through both direct and indirect mechanisms.     

Airborne Pollen Grains of Bozuyuk （Bilecik, Turkey）

Airborne pollen grains in the atmosphere of Bozuyuk were investigated over a 2 yr period from 2000 to 2001 using a Durham sampler. A total number of pollen grains of 5 170 pollen grains belonging to 32 taxa were identified and recorded along with some unidentified pollen grains. Of all the pollen grains, 78.66% were arboreal, 19.20% were non-arboreal, and 2.12% were unidentified. The majority of pollen grains investigated were Pinus, Platanus, Quercus, Cupressaceae, Poaceae, Fagus, Salix, Rosaceae, Urticaceae, Asteraceae, and Chenopodiaceae. The maximum number of pollen grains was recorded in May.     

Polymorphic microsatellites for the study of Aconitum napellus L. (Ranunculaceae), a rare species in France

Aconitum napellus is a perennial European Ranunculaceae that is currently decreasing in France. Six polymorphic microsatellite markers were characterized to study the polymorphism among individuals sampled from six populations in France. The total number of alleles per locus varied from two to four. Mean observed heterozygosities at each microsatellite locus ranged from 0.05 to 0.19. This set of microsatellites offers an efficient tool for more detailed investigations on population genetic structure of a rare species that can reproduce both sexually and by vegetative spread.     

Tubulin glycylases and glutamylases have distinct functions in stabilization and motility of ependymal cilia

Microtubules are subject to a variety of posttranslational modifications that potentially regulate cytoskeletal functions. Two modifications, glutamylation and glycylation, are highly enriched in the axonemes of most eukaryotes, and might therefore play particularly important roles in cilia and flagella. Here we systematically analyze the dynamics of glutamylation and glycylation in developing mouse ependymal cilia and the expression of the corresponding enzymes in the brain. By systematically screening enzymes of the TTLL family for specific functions in ependymal cilia, we demonstrate that the glycylating enzymes TTLL3 and TTLL8 were required for stability and maintenance of ependymal cilia, whereas the polyglutamylase TTLL6 was necessary for coordinated beating behavior. Our work provides evidence for a functional separation of glutamylating and glycylating enzymes in mammalian ependymal cilia. It further advances the elucidation of the functions of tubulin posttranslational modifications in motile cilia of the mammalian brain and their potential importance in brain development and disease.     

Oxytetracycline hydrochloride vital labelling revisited: the case of Dicentrarchus labrax and Diplodus puntazzo

The main objective of this study was to determine the optimal oxytetracycline hydrochloride (OTC) dosage for otolith marking in Dicentrarchus labrax and Diplodus puntazzo. Adult reared individuals of these two species were marked with OTC intraperitoneal injections at three recommended doses (25, 45 and 60 mg kg(-1) fish) and a blank. Fishes were monitored for 36-49 days from when they were marked. The effectiveness of the otolith marking was inversely related to the OTC dosage. The injections were found to have deleterious effects at the highest dosages: (1) mortality was nearly 0% during the first 4 days but then it suddenly rose to 85-100% depending on the fish and treatment, (2) no daily growth increments were formed after marking and (3) no or negative somatic growth was observed. These results suggest that most of the current studies using OTC marking for estimating mortality of wild fishes use an observation period between marking the fishes and releasing that is too short to allow the deleterious effects of OTC to be detected. Species-specific experiments for assessing the long-term mortality should be undertaken when OTC marking is used on wild fishes.