DipA, a pore-forming protein in the outer membrane of lyme disease spirochetes exhibits specificity for the permeation of dicarboxylate

Lyme disease Borreliae are highly dependent on the uptake of nutrients provided by their hosts. Our study describes the identification of a 36 kDa protein that functions as putative dicarboxylate-specific porin in the outer membrane of Lyme disease Borrelia. The protein was purified by hydroxyapatite chromatography from Borrelia burgdorferi B31 and designated as DipA, for dicarboxylate-specific porin A. DipA was partially sequenced, and corresponding genes were identified in the genomes of B. burgdorferi B31, Borrelia garinii PBi and Borrelia afzelii PKo. DipA exhibits high homology to the Oms38 porins of relapsing fever Borreliae. B. burgdorferi DipA was characterized using the black lipid bilayer assay. The protein has a singlechannel conductance of 50 pS in 1 M KCl, is slightly selective for anions with a permeability ratio for cations over anions of 0.57 in KCl and is not voltage-dependent. The channel could be partly blocked by different di- and tricarboxylic anions. Particular high stability constants up to about 28,000 l/mol (in 0.1 M KCl) were obtained among the 11 tested anions for oxaloacetate, 2-oxoglutarate and citrate. The results imply that DipA forms a porin specific for dicarboxylates which may play an important role for the uptake of specific nutrients in different Borrelia species

Complete genome sequence of the uropathogenic methicillin-resistant Staphylococcus aureus strain MRSA-1369

MRSA-1369 is a uropathogenic methicillin-resistant Staphylococcus aureus (MRSA) strain. Here, we present the complete genome sequence of MRSA-1369, which consists of one chromosome (2.87 Mb) and two plasmids (16.68 kb and 3.13 kb). This will serve as a reference genome for future Staphylococcus aureus pathogenesis and multiomic studies

Bit errors in the Kirchhoff-Law–Johnson-Noise secure key exchange

Background: Accuracy in malaria diagnosis and staging is vital in order to reduce mortality and post infectious sequelae. Herein we present a metabolomics approach to diagnostic staging of malaria infection, specifically Plasmodium falciparum infection in children. Methods: A group of 421 patients between six months and six years of age with mild and severe states of malaria with age-matched controls were included in the study, 107, 192 and 122 individuals respectively. A multivariate design was used as basis for representative selection of twenty patients in each category. Patient plasma was subjected to Gas Chromatography-Mass Spectrometry analysis and a full metabolite profile was produced from each patient. In addition, a proof-of-concept model was tested in a Plasmodium berghei in-vivo model where metabolic profiles were discernible over time of infection. Results: A two-component principal component analysis (PCA) revealed that the patients could be separated into disease categories according to metabolite profiles, independently of any clinical information. Furthermore, two sub-groups could be identified in the mild malaria cohort who we believe represent patients with divergent prognoses. Conclusion: Metabolite signature profiling could be used both for decision support in disease staging and prognostication

Knowledge synthesis: Animal health and welfare in organic pig production - Final Report COREPIG

This report reviews the available information on the welfare of pigs when maintained according to organic standards in Europe. It begins by overviewing the populations of organic pigs in different countries at the time of writing (2007), the organic standards which govern their management and the systems in which they are typically kept. It then reviews for each stage in the production cycle (sows, suckling piglets, weaned pigs and fattening pigs) the available literature on health and welfare problems which might be experienced by the animals and the hazards which might give rise to these problems. Finally the report reviews the methods current available for the measurement of pig health and welfare and the extent to which monitoring systems currently exist in different countries, or might be developed. The information gathered in this review formed the basis for the subsequent development of tools for use in a HACCP based management and surveillance system for organic pig herds. These tools will assist the organic pig farmer to prevent selected pig diseases and welfare problems by monitoring and controlling the risk factors. Further details can be found on the COREPIG project website www.icrofs.org/coreorganic/corepig.htm

Study of the protein complex, pore diameter, and pore-forming activity of the Borrelia burgdorferi P13 porin

P13 is one of the major outer membrane proteins of Borrelia burgdorferi. Previous studies described P13 as a porin. In the present study some structure and function aspects of P13 were studied. P13 showed according to lipid bilayer studies a channel-forming activity of 0.6 nanosiemens in 1 m KCl. Single channel and selectivity measurements demonstrated that P13 had no preference for either cations or anions and showed no voltage-gating up to ±100 mV. Blue native polyacrylamide gel electrophoresis was used to isolate and characterize the P13 protein complex in its native state. The complex had a high molecular mass of about 300 kDa and was only composed of P13 monomers. The channel size was investigated using non-electrolytes revealing an apparent diameter of about 1.4 nm with a 400-Da molecular mass cut-off. Multichannel titrations with different substrates reinforced the idea that P13 forms a general diffusion channel. The identity of P13 within the complex was confirmed by second dimension SDS-PAGE, Western blotting, mass spectrometry, and the use of a p13 deletion mutant strain. The results suggested that P13 is the protein responsible for the 0.6-nanosiemens pore-forming activity in the outer membrane of B. burgdorferi

Intercalibration of a concentration McMaster Technique between eight European laboratories

Prior to a European prevalence survey of intestinal parasites of organic pig herds it was decided to introduce one common technique for faecal egg counts and to compare its execution at all involved laboratories to ensure data compatibility. It was clearly shown that avoid confounding variation it is extremely important not only to use identical techniques but also to implement the technique in exactly the same way

Ring-fused 2-pyridones effective against multidrug-resistant Gram-positive pathogens and synergistic with standard-of-care antibiotics

The alarming rise of multidrug-resistant Gram-positive bacteria has precipitated a healthcare crisis, necessitating the development of new antimicrobial therapies. Here we describe a new class of antibiotics based on a ring-fused 2-pyridone backbone, which are active against vancomycin-resistant enterococci (VRE), a serious threat as classified by the Centers for Disease Control and Prevention, and other multidrug-resistant Gram-positive bacteria. Ring-fused 2-pyridone antibiotics have bacteriostatic activity against actively dividing exponential phase enterococcal cells and bactericidal activity against nondividing stationary phase enterococcal cells. The molecular mechanism of drug-induced killing of stationary phase cells mimics aspects of fratricide observed in enterococcal biofilms, where both are mediated by the Atn autolysin and the GelE protease. In addition, combinations of sublethal concentrations of ring-fused 2-pyridones and standard-of-care antibiotics, such as vancomycin, were found to synergize to kill clinical strains of VRE. Furthermore, a broad range of antibiotic resistant Gram-positive pathogens, including those responsible for the increasing incidence of antibiotic resistant healthcare-associated infections, are susceptible to this new class of 2-pyridone antibiotics. Given the broad antibacterial activities of ring-fused 2-pyridone compounds against Gram-positive (GmP) bacteria we term these compounds GmPcides, which hold promise in combating the rising tide of antibiotic resistant Gram-positive pathogens

Иммунологические предикторы отторжения почечного трансплантата в раннем послеоперационном периоде

ПОЧЕК ТРАНСПЛАНТАЦИЯПЕРЕСАДКА ПОЧКИПОЧЕЧНАЯ ТРАНСПЛАНТАЦИЯПОСЛЕОПЕРАЦИОННЫЙ ПЕРИОДТРАНСПЛАНТАЦИОННАЯ ИММУНОЛОГИЯТРАНСПЛАНТАТА ОТТОРЖЕНИЕДЕНДРИТНЫЕ КЛЕТКИДЕНДРИТИЧЕСКИЕ КЛЕТКИLIN-HLA-DR+CD11C+CD123-LIN-HLA-DR+CD11C-CD123+Цель. Выявить иммунологические предикторы отторжения почечного трансплантата в раннем послеоперационном периоде. Материал и методы. Из 197 реципиентов почечного трансплантата были сформированы 3 группы. Группа ПФТ (n=101) – пациенты с удовлетворительной первичной функцией трансплантата. Группа ДФТ (n=82) – пациенты с первичной дисфункцией трансплантата без эпизодов отторжения. Группа ОПТ (n=14) – пациенты с первичной дисфункцией и отторжением почечного трансплантата. Ранняя функция почечного трансплантата оценивалась на 7-е сутки после операции по уровню креатинина крови. При показателях ниже 300 мкмоль/л функция считалась первичной, при значениях, равных или превышающих 300 мкмоль/л, а также при возникновении необходимости в диализе на первой неделе после трансплантации состояние классифицировалось как дисфункция почечного трансплантата. В раннем послеоперационном периоде определяли количество дендритных клеток LIN-HLA-DR+ с фенотипом LIN-HLA-DR+CD11c+CD123- (mDC) и LIN-HLA-DR+CD11c-CD123+ (pDC) в жидкости из дренажа, установленного к почечному трансплантату во время операции. С целью прогнозирования отторжения почечного трансплантата были определены предиктивные характеристики уровня mDC и pDC в дренажной жидкости и выявлены диагностические возможности данного показателя. Результаты. Выявлено, что отторжение почечного трансплантата характеризуется значимым ростом общего числа дендритных клеток (ДК) в дренажной жидкости, преимущественно за счет миелоидных. Определены предиктивные характеристики по уровню миелоидных и плазмацитоидных ДК в дренажной жидкости. Точка отсечения уровня миелоидных дендритных клеток определена на уровне 60,32%, а для плазмацитоидных соответствовала 39,68%. Заключение. При уровне миелоидных дендритных клеток в дренажной жидкости более либо равном 60,32%, а плазмацитоидных менее либо равном 39,68% прогнозируется отторжение почечного трансплантата с чувствительностью 99% и 93% соответственно и специфичностью 89% и 91% соответственно.Objective. To determine the immunological predictors of renal graft rejection in the early postoperative period. Methods. Three groups were formed out of the 197 renal graft recipients. The group PGF (n=101) was made up of patients with satisfactory primary graft function. The group PGD (n = 82) included patients with primary graft dysfunction without episodes of rejection. The group RGR (n=14) consisted of patients with primary dysfunction and renal graft rejection. On the 7th day after transplantation the early kidney graft function was assessed on the basis of serum creatinine levels. When the serum creatinine value was lower than 300 mol/L the function was considered to be primary, at a creatinine concentration was equal to or higher than 300 mol/L, as well as in the case of need for maintenance dialysis on the first week after transplantation, the state was classified as the renal graft dysfunction. In the early postoperative period, the number of LIN-HLA-DR+ dendritic cells with the LIN- HLA-DR+CD11c+CD123- and LIN-HLA-DR+CD11c-CD123+ phenotypes in the fluid from the drainage installed to the kidney graft during surgery was determined. Predictive characteristics of the mDC and pDC levels in the drainage fluid were determined to predict renal graft rejection, and diagnostic capability of this indicator were identified. Results. It has been revealed that renal graft rejection is characterized by a significant growth of the total number of dendritic cells in the drainage fluid, mainly due to myeloid ones. Predictive characteristics were determined by the level of myeloid and plasmacytoid dendritic cells in the drainage fluid. The cut-off point of the level of myeloid dendritic cells was determined at the level of 60.32%, and for plasmacytoid dendritic cells it corresponded to 39.68%. Conclusion. With the level of myeloid dendritic cells in the drainage fluid greater or equal 60.32%, and plasmacytoid cells lower or equal 39.68%, renal graft rejection is predicted with a sensitivity of 99% and 93%, respectively, and a specificity of 89% and 91%, respectively