Pseudomonas aeruginosa Disrupts Caenorhabditis elegans Iron Homeostasis, Causing a Hypoxic Response and Death

SummaryThe opportunistic pathogen Pseudomonas aeruginosa causes serious human infections, but effective treatments and the mechanisms mediating pathogenesis remain elusive. Caenorhabditis elegans shares innate immune pathways with humans, making it invaluable to investigate infection. To determine how P. aeruginosa disrupts host biology, we studied how P. aeruginosa kills C. elegans in a liquid-based pathogenesis model. We found that P. aeruginosa-mediated killing does not require quorum-sensing pathways or host colonization. A chemical genetic screen revealed that iron chelators alleviate P. aeruginosa-mediated killing. Consistent with a role for iron in P. aeruginosa pathogenesis, the bacterial siderophore pyoverdin was required for virulence and was sufficient to induce a hypoxic response and death in the absence of bacteria. Loss of the C. elegans hypoxia-inducing factor HIF-1, which regulates iron homeostasis, exacerbated P. aeruginosa pathogenesis, further linking hypoxia and killing. As pyoverdin is indispensable for virulence in mice, pyoverdin-mediated hypoxia is likely to be relevant in human pathogenesis

Influence of mammal fossorial activity on the soil fermentative activity in conditions of metallurgical production

Изучалось влияние роющей активности микромаммалий как экологического фактора в интенсификации почвообразования. Рассматривалась ферментативная активность почвы – ее способность проявлять каталитическое воздействие на превращения различных соединений под воздействием имеющихся в ней ферментов. Показана изменчивость уреазной активности почв в условиях техногенеза при участии животных. Установлено ee положительное влияние на ферментативную активность исследованных почв. Определены показатели, статистически достоверно влияющие на изменение активности уреазы в почве. Вивчено вплив рийної активності мікромамалій як екологічного чинника інтенсифікації ґрунтоутворення. Розглянуто ферментативну активність ґрунту – його здатність проявляти каталітичний вплив на перетворення різних хімічних сполук під впливом ферментів, які містяться в ньому. Визначено зміни уреазної активності ґрунтів в умовах техногенезу за участю тварин. З’ясовано позитивний вплив рийної активності ссавців-ґрунториїв на ферментативну активність досліджуваних ґрунтів. Установлено показники, які статистично достовірно впливають на зміну уреазної активності в ґрунті. Effect of mammal fossorial activity as an ecological factor of the soil genesis intensification is studied. Enzymatic activity of soil as its ability to demonstrate a catalytic effect for various compounds transformation is examined. Variability of soil urease activity in technogenic conditions with the participation of animals is shown. The positive influence of animals’ activity on the catalitic ability of the investigated soils was determined. The statistically significant characteristics which have an influence on the urease activity in soil are found out

INFLUENCE OF GLICEROL ON FUNCTIONAL-MORPHOLOGICAL INDICATORS OF KIDNEYS AT MODELLING RENAL INSUFFICIENCY IN RATS

It is known, that after acute damage of kidney there is a risk of development of chronic kidney desease and death rate from its complications. Material and methods. Research are spent on 40 not purebred rats at modelling of acute damage of the kidneys caused by toxic doses of glycerol. To evaluate histopathologal changes , we used cuts of fabrics painted gematoksilin- eozinom. Ultrathin preparations analyzed in electronic microscope PЕМ-125К. Results. Administration of glycerol leads to uremia with dystrophic changes in tubular device and glomerular hypertrophy. At a stage of chronic renal insufficiency reduction of the glomerular sizes, tubulointerstitial fibrosis and glomerulosclerosis is observed. Conclusion. At modelling of a nephritic pathology by introduction of 50 % glycerol infringement of function of kidneys has phasic character with probable development of chronic kidney desease in 8 weeks

MORPHOLOGICAL AND FUNCTIONAL STATE OF ENDOTHELIUM AT PATIENTS WITH CORONARY ARTERY DISEASE AND CHRONIC GLOMERULONEFRITIS

All over the world the increase in quantity of patients with vascular complications of chronic inflammatory diseases of kidneys is marked. The interrelation of morphological and biochemical markers of atherosclerotic lesions were studied in 41 patients with coronary artery disease (CAD) (group 1) and 62 - with CAD and chronic glomerulonephritis (CGN) (group 2). An extracranial carotid artery (CA) status was investigated by duplex ultrasonography. VE-cadherin content determined by ELISA. States of the antioxidant system was evaluated by the concentration of malondialdehyde (MDA) and sulfhydryl groups (SH-groups) in the blood plasma by the photometric method. The levels of nitric oxide stable metabolites – NO2 and total (NO2+NO3) in plasma was determined by the photometric method. There was found that the frequency of CA plaques detection in groups 1 and 2 did not differ (27,6% and 31,0%, respectively), but patients of group 2 were reliably younger. Pronounced VE-cadherin increase (3,6-fold, p <0,01) at the background of the deterioration of renal function (2,24 -fold GFR decrease, and urinary protein excretion reaches (0,200,98) g / day) was observed in group 2. The content of NO2 in group 2 was significantly lower than in controls, and total (NO2+NO3) was increased as compared with control (2,40-fold, P <0,01), and with patients of group 1 (in 1,86-fold, p <0.05). Increase of MDA level in patients of group 2 (2,61-fold, P<0,01) accompanied by reduction of SH groups content – by 25,2% (P <0.05) compared with control. Thus, in patients with combined pathology revealed the most pronounced disorders of endothelial integrity and function, which was worsening by imbalance in the pro-antioxidant system. Accelerated atherosclerotic vascular changes in these patients are probably related to the chronic inflammatory process

Imaging biomarkers in prostate cancer: role of PET/CT and MRI

Prostate-specific antigen (PSA) is currently the most widely used biomarker of prostate cancer (PCa). PSA suggests the presence of primary tumour and disease relapse after treatment, but it is not able to provide a clear distinction between locoregional and distant disease. Molecular and functional imaging, that are able to provide a detailed and comprehensive overview of PCa extension, are more reliable tools for primary tumour detection and disease extension assessment both in staging and restaging. In the present review we evaluate the role of PET/CT and MRI in the diagnosis, staging and restaging of PCa, and the use of these imaging modalities in prognosis, treatment planning and response assessment. Innovative imaging strategies including new radiotracers and hybrid scanners such as PET/MRI are also discussed

WormBase 2007

WormBase (www.wormbase.org) is the major publicly available database of information about Caenorhabditis elegans, an important system for basic biological and biomedical research. Derived from the initial ACeDB database of C. elegans genetic and sequence information, WormBase now includes the genomic, anatomical and functional information about C. elegans, other Caenorhabditis species and other nematodes. As such, it is a crucial resource not only for C. elegans biologists but the larger biomedical and bioinformatics communities. Coverage of core areas of C. elegans biology will allow the biomedical community to make full use of the results of intensive molecular genetic analysis and functional genomic studies of this organism. Improved search and display tools, wider cross-species comparisons and extended ontologies are some of the features that will help scientists extend their research and take advantage of other nematode species genome sequences

Methodological framework for radiomics applications in Hodgkin’s lymphoma

Background: According to published data, radiomics features differ between lesions of refractory/relapsing HL patients from those of long-term responders. However, several methodological aspects have not been elucidated yet. Purpose: The study aimed at setting up a methodological framework in radiomics applications in Hodgkin’s lymphoma (HL), especially at (a) developing a novel feature selection approach, (b) evaluating radiomic intra-patient lesions’ similarity, and (c) classifying relapsing refractory (R/R) vs non-(R/R) patients. Methods: We retrospectively included 85 patients (male:female = 52:33; median age 35 years, range 19–74). LIFEx (www.lifexsoft.org) was used for [18F]FDG-PET/CT segmentation and feature extraction. Features were a-priori selected if they were highly correlated or uncorrelated to the volume. Principal component analysis-transformed features were used to build the fingerprints that were tested to assess lesions’ similarity, using the silhouette. For intra-patient similarity analysis, we used patients having multiple lesions only. To classify patients as non-R/R and R/R, the fingerprint considering one single lesion (fingerprint_One) and all lesions (fingerprint_All) was tested using Random Undersampling Boosting of Tree Ensemble (RUBTE). Results: HL fingerprints included up to 15 features. Intra-patient lesion similarity analysis resulted in mean/median silhouette values below 0.5 (low similarity especially in the non-R/R group). In the test set, the fingerprint_One classification accuracy was 62% (78% sensitivity and 53% specificity); the classification by RUBTE using fingerprint_All resulted in 82% accuracy (70% sensitivity and 88% specificity). Conclusions: Lesion similarity analysis was developed, and it allowed to demonstrate that HL lesions were not homogeneous within patients in terms of radiomics signature. Therefore, a random target lesion selection should not be adopted for radiomics applications. Moreover, the classifier to predict R/R vs non-R/R performed the best when all the lesions were used

Methodological framework for radiomics applications in Hodgkin’s lymphoma

According to published data, radiomics features differ between lesions of refractory/relapsing HL patients from those of long-term responders. However, several methodological aspects have not been elucidated yet. The study aimed at setting up a methodological framework in radiomics applications in Hodgkin’s lymphoma (HL), especially at (a) developing a novel feature selection approach, (b) evaluating radiomic intra-patient lesions’ similarity, and (c) classifying relapsing refractory (R/R) vs non-(R/R) patients. We retrospectively included 85 patients (male:female = 52:33; median age 35 years, range 19–74). LIFEx (www.lifexsoft.org) was used for [18F]FDG-PET/CT segmentation and feature extraction. Features were a-priori selected if they were highly correlated or uncorrelated to the volume. Principal component analysis transformed features were used to build the fingerprints that were tested to assess lesions’ similarity, using the silhouette. For intra-patient similarity analysis, we used patients having multiple lesions only. To classify patients as non-R/R and R/R, the fingerprint considering one single lesion (fingerprint_One) and all lesions (fingerprint_All) was tested using Random Undersampling Boosting of Tree Ensemble (RUBTE). HL fingerprints included up to 15 features. Intra-patient lesion similarity analysis resulted in mean/median silhouette values below 0.5 (low similarity especially in the non-R/R group). In the test set, the fingerprint_One classification accuracy was 62% (78% sensitivity and 53% specificity); the classification by RUBTE using fingerprint_All resulted in 82% accuracy (70% sensitivity and 88% specificity). Lesion similarity analysis was developed, and it allowed to demonstrate that HL lesions were not homogeneous within patients in terms of radiomics signature. Therefore, a random target lesion selection should not be adopted for radiomics applications. Moreover, the classifier to predict R/R vs non-R/R performed the best when all the lesions were used