The Lectin Pathway of Complement Activation Is a Critical Component of the Innate Immune Response to Pneumococcal Infection

The complement system plays a key role in host defense against pneumococcal infection. Three different pathways, the classical, alternative and lectin pathways, mediate complement activation. While there is limited information available on the roles of the classical and the alternative activation pathways of complement in fighting streptococcal infection, little is known about the role of the lectin pathway, mainly due to the lack of appropriate experimental models of lectin pathway deficiency. We have recently established a mouse strain deficient of the lectin pathway effector enzyme mannan-binding lectin associated serine protease-2 (MASP-2) and shown that this mouse strain is unable to form the lectin pathway specific C3 and C5 convertases. Here we report that MASP-2 deficient mice (which can still activate complement via the classical pathway and the alternative pathway) are highly susceptible to pneumococcal infection and fail to opsonize Streptococcus pneumoniae in the none-immune host. This defect in complement opsonisation severely compromises pathogen clearance in the lectin pathway deficient host. Using sera from mice and humans with defined complement deficiencies, we demonstrate that mouse ficolin A, human L-ficolin, and collectin 11 in both species, but not mannan-binding lectin (MBL), are the pattern recognition molecules that drive lectin pathway activation on the surface of S. pneumoniae. We further show that pneumococcal opsonisation via the lectin pathway can proceed in the absence of C4. This study corroborates the essential function of MASP-2 in the lectin pathway and highlights the importance of MBL-independent lectin pathway activation in the host defense against pneumococci

What was retained? The assessment of the training for the peer trainers' course on short and long term basis

<p>Abstract</p> <p>Background</p> <p>In Turkey, the studies have reported that the age at which sexual intercourse and sexual activity starts has been steadily declining. There is an urgent need to increase social and health services for young people in order to provide them with a healthy life by changing their risky behaviors, avoiding unwanted pregnancies and sexually transmitted diseases (STDs). Sexual and reproductive health training particularly for adolescents warrants special attention and consideration.</p> <p>The objective of our study is to find out the short and long term effectiveness of a training course on peer education.</p> <p>Methods</p> <p>The study was conducted on 237 students who participated in a 40 hour Peer Trainer Training course. We utilized two types of evaluation methods to measure the effectiveness of the training on students' knowledge and attitude. The first method consisted of administering 3 tests comprised of the same 45 questions at 3 separate time intervals. Prior to the training a pre-test was given to obtain a measurement of base knowledge, and then an immediate post-test was given to evaluate the change in the knowledge and opinion of the participants.</p> <p>Finally, 6 months later the same test was administered to measure the retention of knowledge by the students. In the second type of evaluation, the participants' assessment of the training itself was sought by asking them to complete a Short Course Evaluation Form. We utilized SPSS 12.0 for descriptive analysis, and the Wilcoxon two related sample t-test were run.</p> <p>Results</p> <p>According to the pre and immediate post-test results, the training resulted in an increase in knowledge learned by an average of 21.6% (p < 0.05). Whereas, according to the immediate post test and the late post-test which was given six month later, there was a 1.8% decrease in the knowledge and attitude of the participants (p > 0.05). Participants thought that they had fun during training, and they became aware of what they knew and what they did not know.</p> <p>Conclusion</p> <p>Peer trainers with the training methods utilized, the knowledge and counseling acquired during training sessions will be able to provide counseling to their peers on reproductive health.</p

Alternatives to antibiotics-a pipeline portfolio review

Antibiotics have saved countless lives and enabled the development of modern medicine over the past 70 years. However, it is clear that the success of antibiotics might only have been temporary and we now expect a long-term and perhaps never-ending challenge to find new therapies to combat antibiotic-resistant bacteria. A broader approach to address bacterial infection is needed. In this Review, we discuss alternatives to antibiotics, which we defined as non-compound approaches (products other than classic antibacterial agents) that target bacteria or any approaches that target the host. The most advanced approaches are antibodies, probiotics, and vaccines in phase 2 and phase 3 trials. This first wave of alternatives to antibiotics will probably best serve as adjunctive or preventive therapies, which suggests that conventional antibiotics are still needed. Funding of more than £1·5 billion is needed over 10 years to test and develop these alternatives to antibiotics. Investment needs to be partnered with translational expertise and targeted to support the validation of these approaches in phase 2 trials, which would be a catalyst for active engagement and investment by the pharmaceutical and biotechnology industry. Only a sustained, concerted, and coordinated international effort will provide the solutions needed for the future.</p

What is the effectiveness of surgical and non-surgical therapies in the treatment of ischemic priapism in patients with sickle cell disease? A systematic review by the EAU Sexual and Reproductive Health Panel

The authors acknowledge the participants for their cooperation Conflict of Interest: None of the authors declare any interest. Formatting of funding sources: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.Peer reviewedPostprin

Amplification of cox2 (∼620 bp) from 2 mg of Up to 129 Years Old Herbarium Specimens, Comparing 19 Extraction Methods and 15 Polymerases

During the past years an increasing number of studies have focussed on the use of herbarium specimens for molecular phylogenetic investigations and several comparative studies have been published. However, in the studies reported so far usually rather large amounts of material (typically around 100 mg) were sampled for DNA extraction. This equals an amount roughly equivalent to 8 cm2 of a medium thick leaf. For investigating the phylogeny of plant pathogens, such large amounts of tissue are usually not available or would irretrievably damage the specimens. Through systematic comparison of 19 DNA extraction protocols applied to only 2 mg of infected leaf tissue and testing 15 different DNA polymerases, we could successfully amplify a mitochondrial DNA region (cox2; ∼620 bp) from herbarium specimens well over a hundred years old. We conclude that DNA extraction and the choice of DNA polymerase are crucial factors for successful PCR amplification from small samples of historic herbarium specimens. Through a combination of suitable DNA extraction protocols and DNA polymerases, only a fraction of the preserved plant material commonly used is necessary for successful PCR amplification. This facilitates the potential use of a far larger number of preserved specimens for molecular phylogenetic investigation and provides access to a wealth of genetic information in preserved in specimens deposited in herbaria around the world without reducing their scientific or historical value

The equilibria that allow bacterial persistence in human hosts

We propose that microbes that have developed persistent relationships with human hosts have evolved cross-signalling mechanisms that permit homeostasis that conforms to Nash equilibria and, more specifically, to evolutionarily stable strategies. This implies that a group of highly diverse organisms has evolved within the changing contexts of variation in effective human population size and lifespan, shaping the equilibria achieved, and creating relationships resembling climax communities. We propose that such ecosystems contain nested communities in which equilibrium at one level contributes to homeostasis at another. The model can aid prediction of equilibrium states in the context of further change: widespread immunodeficiency, changing population densities, or extinctions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62883/1/nature06198.pd