Inhibition of Inducible Nitric Oxide Synthase Prevents IL-1β-Induced Mitochondrial Dysfunction in Human Chondrocytes

Interleukin (IL)-1β is an important pro-inflammatory cytokine in the progression of osteoarthritis (OA), which impairs mitochondrial function and induces the production of nitric oxide (NO) in chondrocytes. The aim was to investigate if blockade of NO production prevents IL-1βinduced mitochondrial dysfunction in chondrocytes and whether cAMP and AMP-activated protein kinase (AMPK) affects NO production and mitochondrial function. Isolated human OA chondrocytes were stimulated with IL-1β in combination with/without forskolin, L-NIL, AMPK activator or inhibitor. The release of NO, IL-6, PGE2 , MMP3, and the expression of iNOS were measured by ELISA or Western blot. Parameters of mitochondrial respiration were measured using a seahorse analyzer. IL-1β significantly induced NO release and mitochondrial dysfunction. Inhibition of iNOS by L-NIL prevented IL-1β-induced NO release and mitochondrial dysfunction but not IL-1β-induced release of IL-6, PGE2 , and MMP3. Enhancement of cAMP by forskolin reduced IL-1β-induced NO release and prevented IL-1β-induced mitochondrial impairment. Activation of AMPK increased IL-1β-induced NO production and the negative impact of IL-1β on mitochondrial respiration, whereas inhibition of AMPK had the opposite effects. NO is critically involved in the IL-1β-induced impairment of mitochondrial respiration in human OA chondrocytes. Increased intracellular cAMP or inhibition of AMPK prevented both IL-1β-induced NO release and mitochondrial dysfunction

2D-fluoroscopic navigated percutaneous screw fixation of pelvic ring injuries - a case series

<p>Abstract</p> <p>Background</p> <p>Screw fixation of pelvic ring fractures is a common, but demanding procedure and navigation techniques were introduced to increase the precision of screw placement. The purpose of this case series was the evaluation of screw misplacement rate and functional outcome of percutaneous screw fixation of pelvic ring disruptions using a 2D navigation system.</p> <p>Methods</p> <p>Between August 2004 and December 2007, 44 of 442 patients with pelvic injuries were included for closed reduction and percutaneous screw fixation of disrupted pelvic ring lesions using an optoelectronic 2D-fluoroscopic based navigation system. Operating and fluoroscopy time were measured, as well as peri- and postoperative complications documented. Screw position was assessed by postoperative CT scans. Quality of live was evaluated by SF 36-questionnaire in 40 of 44 patients at mean follow up 15.5 ± 1.2 month.</p> <p>Results</p> <p>56 iliosacral- and 29 ramus pubic-screws were inserted (mean operation time per screw 62 ± 4 minutes, mean fluoroscopy time per screw 123 ± 12 seconds). In post-operative CT-scans the screw position was assessed and graded as follows: I. secure positioning, completely in the cancellous bone (80%); II. secure positioning, but contacting cortical bone structures (14%); III. malplaced positioning, penetrating the cortical bone (6%). The malplacements predominantly occurred in bilateral overlapping screw fixation. No wound infection or iatrogenic neurovascular damage were observed. Four re-operations were performed, two of them due to implant-misplacement and two of them due to implant-failure.</p> <p>Conclusion</p> <p>2D-fluoroscopic navigation is a safe tool providing high accuracy of percutaneous screw placement for pelvic ring fractures, but in cases of a bilateral iliosacral screw fixation an increased risk for screw misplacement was observed. If additional ramus pubic screw fixations are performed, the retrograde inserted screws have to pass the iliopubic eminence to prevent an axial screw loosening.</p

Timing is everything: the regulation of type III secretion

Type Three Secretion Systems (T3SSs) are essential virulence determinants of many Gram-negative bacteria. The T3SS is an injection device that can transfer bacterial virulence proteins directly into host cells. The apparatus is made up of a basal body that spans both bacterial membranes and an extracellular needle that possesses a channel that is thought to act as a conduit for protein secretion. Contact with a host-cell membrane triggers the insertion of a pore into the target membrane, and effectors are translocated through this pore into the host cell. To assemble a functional T3SS, specific substrates must be targeted to the apparatus in the correct order. Recently, there have been many developments in our structural and functional understanding of the proteins involved in the regulation of secretion. Here we review the current understanding of protein components of the system thought to be involved in switching between different stages of secretion

The Acinetobacter baumannii website (Ab-web): a multidisciplinary knowledge hub, communication platform, and workspace

Acinetobacter baumannii is a Gram-negative bacterium increasingly implicated in hospital-acquired infections and outbreaks. Effective prevention and control of such infections are commonly challenged by the frequent emergence of multidrug-resistant strains. Here we introduce Ab-web (https://www.acinetobacterbaumannii.no), the first online platform for sharing expertise on A. baumannii. Ab-web is a species-centric knowledge hub, initially with ten articles organized into two main sections, ‘Overview’ and ‘Topics’, and three themes, ‘epidemiology’, ‘antibiotic resistance’, and ‘virulence’. The ‘workspace’ section provides a spot for colleagues to collaborate, build, and manage joint projects. Ab-web is a community-driven initiative amenable to constructive feedback and new ideas

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)

The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes and functional assays of all major human and murine immune cell subsets. Notably, the Guidelines contain helpful tables highlighting phenotypes and key differences between human and murine cells. Another useful feature of this edition is the flow cytometry analysis of clinical samples with examples of flow cytometry applications in the context of autoimmune diseases, cancers as well as acute and chronic infectious diseases. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid. All sections are written and peer‐reviewed by leading flow cytometry experts and immunologists, making this edition an essential and state‐of‐the‐art handbook for basic and clinical researchers.DFG, 389687267, Kompartimentalisierung, Aufrechterhaltung und Reaktivierung humaner Gedächtnis-T-Lymphozyten aus Knochenmark und peripherem BlutDFG, 80750187, SFB 841: Leberentzündungen: Infektion, Immunregulation und KonsequenzenEC/H2020/800924/EU/International Cancer Research Fellowships - 2/iCARE-2DFG, 252623821, Die Rolle von follikulären T-Helferzellen in T-Helferzell-Differenzierung, Funktion und PlastizitätDFG, 390873048, EXC 2151: ImmunoSensation2 - the immune sensory syste

T.: Illumination invariant color texture analysis based on sum- and difference-histograms

Abstract. Color texture algorithms have been under investigation for quite a few years now. However, the results of these algorithms are still under considerable influence of the illumination conditions under which the images were captured. It is strongly desireable to reduce the influence of illumination as much as possible to obtain stable and satisfying classification results even under difficult imaging conditions, as they can occur e.g. in medical applications like endoscopy. In this paper we present the analysis of a well-known texture analysis algorithm, namely the sumand difference-histogram features, with respect to illumination changes. Based on this analysis, we propose a novel set of features factoring out the illumination influence from the majority of the original features. We conclude our paper with a quantitative, experimental evaluation on artificial and real image samples.

Top 10 der 100 Mittwochstipps bei Franco-Fil - oder waren es nur 99?

Am 17. Juli 2013 starteten wir bei Franco-Fil mit dem Mittwochstipp 1 - Dictionnaires d’autrefois – French dictionaries of the 17th, 18th, 19th and 20th centuries. Dreieinhalb Jahre später sind wir beim Mittwochstipp 100 angelangt, Zeit also für einen kurzen Rückblick auf die zehn meistgelesenen Tipps in dieser Serie. Diese nahm zunächst auf dem Facebook-Account des DHIP mit eigenständigen Postings jeden Mittwoch ihren Anfang. Um die Tipps dauerhaft zu speichern, sind wir 2013 auf unser Blog ..

Acinetobacter equi sp. nov., isolated from horse faeces

The taxonomic position of five strains isolated from horse faeces, and which shared identical 16S rRNA gene sequences, were studied. Cells of all isolates are Gram-stain-negative, obligately aerobic and have a rod-shaped appearance. The strains show highest 16S rRNA gene sequence similarities to Acinetobacter lwoffii (98.3 %), Acinetobacter haemolyticus (98.0 %), Acienetobacter johnsonii (97.9 %) and Acinetobacter brisouii (97.9 %). Whole-genome sequencing of strain 114T and phylogeny reconstruction based on a core set of 1061 Acinetobacter genes indicated that A. bouvetii CIP 107468T was the closest relative among species of the genus Acinetobacter for which whole genome sequences are available. The genomic DNA G+C content of strain 114T is 34.9 mol%, which is lower than any other value reported for the genus Acinetobacter. The predominant polyamine is 1,3-diaminopropane, which is typical for the genus Acinetobacter. The most abundant fatty acids are C16 : 1ω7c and/or iso-C15 : 0 2-OH (36 %) and C16 : 0 (28 %). The proportion of C18 : 1ω9c (7 %) is distinctively low compared to most species of the genus. The major ubiquinone of strain 114T is Q-9. Microscopic studies revealed the presence of pili and the absence of flagella. The capability of all five strains to utilize l-arabinose and gentisate as well as their lack of growth at temperatures of 41 °C and above provide sufficient criteria to distinguish the isolates from all species of the genus Acinetobacter with validly published names. Based on these combined data, the five isolates represent a novel species of the genus Acinetobacter, for which the name Acinetobacter equi sp. nov. is proposed. The type strain is 114T ( = DSM 27228T = CCUG 65204T)