Interleukin‐21 administration to aged mice rejuvenates their peripheral T‐cell pool by triggering de novo thymopoiesis

The vaccination efficacy in the elderly is significantly reduced compared to younger populations due to thymic involution and age‐related intrinsic changes affecting their naïve T‐cell compartment. Interleukin (IL)‐21 was recently shown to display thymostimulatory properties. Therefore, we hypothesized that its administration to ageing hosts may improve T‐cell output and thus restore a competent peripheral T‐cell compartment. Indeed, an increase in the production of recent thymic emigrants (RTEs) attributable to intrathymic expansion of early thymic progenitors (ETPs), double‐negative (DN), and double‐positive (DP) thymocytes as well as thymic epithelial cell (TEC) was observed in recombinant (r)IL‐21‐treated aged mice. In sharp contrast, no alterations in the frequency of bone marrow (BM)‐derived progenitors were detected following rIL‐21 administration. Enhanced production of naïve T cells improved the T‐cell receptor (TCR) repertoire diversity and re‐established a pool of T cells exhibiting higher levels of miR‐181a and diminished amounts of the TCR‐inhibiting phosphatases SHP‐2 and DUSP5/6. As a result, stimulation of T cells derived from rIL‐21‐treated aged mice displayed enhanced activation of Lck, ZAP‐70, and ERK, which ultimately boosted their IL‐2 production, CD25 expression, and proliferation capabilities in comparison with T cells derived from control aged mice. Consequently, aged rIL‐21‐treated mice vaccinated using a tyrosinase‐related protein 2 (Trp2)‐derived peptide exhibited a substantial delay in B16 tumor growth and improved survival. The results of this study highlight the immunorestorative function of rIL‐21 paving its use as a strategy for the re‐establishment of effective immunity in the elderly.     

Interaction of FtsA and PBP3 proteins in the Escherichia coli septum.

Mutations in the ftsA gene of Escherichia coli conferred a higher resistance to lysis induced by penicillin or by a combination of cefsulodin and furazlocillin. The ftsA2 allele codes for an FtsA protein which is inactive at 42 degrees C but is able to regain its activity once it is transferred back to 30 degrees C; ftsA2 filaments formed at 42 degrees C in the presence of penicillin divided once the penicillin was removed and the temperature was lowered to 30 degrees C. Potential septation sites in the filaments of wild-type cells treated in the same way remained inactive. The binding of a radioactively labeled derivative of ampicillin to penicillin-binding protein 3 (PBP3) was significantly decreased in strain D-3, containing the mutant allele ftsA3, when the binding assay was performed at the restrictive temperature. A molecular species able to cross-react with an anti-PBP3 serum was nevertheless found to be present in the envelope of D-3 cells. These observations suggested that the FtsA protein, a protein with a structural and regulatory role in septation, and PBP3, a protein enzymatically active in the synthesis of murein for septation, interact with each other.     

The ftsA gene product participates in formation of the Escherichia coli septum structure.

The patterns of septation in filaments of Escherichia coli, formed as a consequence of the lack of an active ftsA gene product and then returned to permissive conditions, were analyzed in isogenic strains containing three different mutated alleles of ftsA. Septation was blocked for at least one doubling time at the potential septation sites that presumably contained inactive FtsA protein but not at those sites containing either the active gene product or no gene product at all. These results suggested a possible structural role for the ftsA gene product in the construction of the E. coli septum.     

Prevalencia de obesidad y riesgo cardiovascular asociado en la población general de un área de salud de Extremadura. Estudio Hermex

Introduction and objectivesTo estimate the prevalence of obesity and its associated cardiovascular risk in the general population of a health area in Extremadura.Materials and methodsA cross-sectional study on a random population sample aged 25-79 years from the Don Benito-Villanueva (Badajoz) health area. Risk factors and cardiovascular disease were examined. Anthropometric and blood pressure measurements were collected, and a blood sample was taken. Obese subjects were categorized into different risk levels as proposed by the Spanish Society for the Study of Obesity, and the influence of obesity on estimation of the risk of ischemic heart disease was studied using the Framingham function, as adapted for Spain.ResultsA total of 2833 of the 3521 subjects screened (80.5%) participated in the study. Mean age was 51.2 years (SD 14.7), and 46.5% were males. Male subjects had a greater prevalence of overweight and obesity (46.2% and 37.7% respectively) as compared to females (37.7% and 32.6%) (p<0.005 and p<0.05 respectively). Only 10% of obese subjects had no increased cardiovascular risk. Obesity was associated to an 8-fold increase in the presence of a high risk for ischemic heart disease in females (p<0.001), as compared to a 1.4-fold increase in males (p=0.095).ConclusionsObesity is highly prevalent and affects, together with overweight, 74.1% of the population in an Extremadura health area. A vast majority of obese subjects have an increased cardiovascular risk, which is very marked for ischemic heart disease in females.     

Bacterial diversity from benthic mats of Antarctic lakes as a source of new bioactive metabolites

During the MICROMAT project, the bacterial diversity of microbial mats growing in the benthic environment of Antarctic lakes was accessed for the discovery of novel antibiotics. In all, 723 Antarctic heterotrophic bacteria belonging to novel and/or endemic taxa in the α-, β- and γ-subclasses of the Proteobacteria, the Bacteroidetes branch, and of the high and low percentage G+C Gram-positives, were isolated, cultivated in different media and at different temperatures, and then screened for the production of antimicrobial activities. A total of 6348 extracts were prepared by solid phase extraction of the culture broths or by biomass solvent extraction. 122 bacteria showed antibacterial activity against the Gram-positives Staphylococcus aureus and to a lower extent Enterococcus faecium, and versus the Gram-negative Escherichia coli. Few of these strains showed also some antifungal activity against Cryptococcus neoformans, Aspergillus fumigatus and to a lower extent Candida albicans. LC–MS fractionation of extracts from a subset of strains (hits) that exhibited relatively potent antibacterial activities evidenced a chemical novelty that was further investigated. Two strains of Arthrobacter agilis produced potent antibacterial compounds with activity against Gram-positives and possibly related to novel cyclic thiazolyl peptides. To our knowledge, this is the first report of new antibiotics produced by bacteria from benthic microbial mats from Antarctic lakes. With no doubts these microbial assemblages represent an extremely rich source for the isolation of new strains producing novel bioactive metabolites with the potential to be developed as antibiotic compounds.     

Native Species for Roadslope Revegetation: Selection,Validation, and Cost Effectiveness

Native species arise as an alternative to improve the poor success of traditional hydroseeding with commercial species in degraded areas. The objectives of this study were to (1) establish a procedure to select suitable native species for roadslope revegetation, (2) validate the procedure by means of field sowing experiments, and (3) assess cost effectiveness of the use of native species in hydroseeding as regards commercial ones. Vegetation surveys were performed in semiarid roadslopes of East Spain and species success evaluated according to abundance and frequency. A list of potentially suitable species for revegetation was produced and a subset of species selected and hydroseeded to check their suitability in hydroseeding. Cost effectiveness of the use of native species was estimated. Results support the suitability of the procedure for the selection of native species. Vegetation cover produced by the hydroseeded mixture of native species was high (between 43 and 70% throughout the 4 years) and was 4–20 times higher than the cover produced by a standard commercial seed mixture. The price of the selected seed mixture was 30 times that of the commercial one, but the cost of relevant ecological advantages provided by the use of native species was only twice that of the commercial species on the basis of cost effectiveness assessment. Practical consequences for restorers, policymakers, and practitioners are discussed, and the use of native species is encouraged to improve revegetation success of roadslopes and similar slope types especially in semiarid and arid environments.     

Polymorphism in the yclC-rpoS region of enterobacteria

The nucleotide sequence downstream from the rpoS gene in Enterobacter cloacae and Kluyvera cryocrescens contains the slyA-pad1-yclC genes. The DNA sequence of Enterobacter cloacae CETC960 shows a 2.6-kb insertion of unknown origin between rpoS and slyA. This 2.6-kb sequence has also been detected in species of Salmonella and in Pseudomonas aeruginosa, but not in the same location. This insertion has been detected in all the Enterobacter cloacae clinical strains studied although the size of the rpoS-yclC region was highly variable, possibly owing to the presence of insertions and/or deletions. The study of the rpoS-mutS region in other enterobacteria also showed variability in size. Our results support the idea of a variational hot spot in the rpoS-mutS region that could be related to pathogenesis and horizontal transfer.     

Sip,an integrase protein with excision,circularization and integration activities,defines a new family of mobile Staphylococcus aureus pathogenicity islands

We report the complete sequence of Staphylococcal pathogenicity island bovine 2 (SaPIbov2), encoding the biofilm-associated protein Bap. SaPIbov2 contains 24 open reading frames, including sip, which encodes a functional staphylococcal integrase protein. SaPIbov2 is bordered by 18 bp direct repeats. The integration site into the chromosome lies at the 3' end of a gene encoding GMP synthase. SaPIbov2 has extensive similarity to previously described pathogenicity islands of Staphylococcus aureus. The principal difference is that toxin genes present in the other pathogenicity islands are exchanged for a transposon-like element that carries the bap gene and genes encoding an ABC transporter and a transposase. Also, SaPIbov2 can be excised to form a circular element and can integrate site-specifically and RecA-independently at a chromosomal att site in a Sip-dependent manner. This was demonstrated both in S. aureus and with plasmid substrates ectopically in Escherichia coli. Thus, SaPIbov2 encodes a functional recombinase of the integrase family that promotes element excision and insertion/integration. In addition, we demonstrated that the presence of SaPIbov2 facilitated the persistence of S. aureus in an intramammary gland infection model. Finally, different bovine isolates of S. aureus were found to carry islands related to SaPIbov2, suggesting the existence of a family of related pathogenicity islands.     

HPLC studio: a novel software utility to perform HPLC chromatogram comparison for screening purposes

A new tool, HPLC Studio, was developed for the comparison of high-performance liquid chromatography (HPLC) chromatograms from microbial extracts. The new utility makes it possible to create a virtual chromatogram by mixing up to 20 individual chromatograms. The virtual chromatogram is the first step in establishing a ranking of the microbial fermentation conditions based on either the area or diversity of HPLC peaks. The utility was used to maximize the diversity of secondary metabolites tested from a microorganism and therefore increase the chances of finding new lead compounds in a drug discovery program.