Association between Periodontal Disease and Inflammatory Arthritis Reveals Modulatory Functions by Melanocortin Receptor Type 3

Supported by Medical Research Council grant MR/K013068/1 (M.P. and T.M.M.), William Harvey Research Foundation (M.P. and L.V.N.), and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq M.F.M.M., T.A.dS.; Brazil)

Detection of Vibrio cholerae and Acanthamoeba species from same natural water samples collected from different cholera endemic areas in Sudan

<p>Abstract</p> <p>Background</p> <p><it>Vibrio cholerae </it>O1 and <it>V. cholerae </it>O139 infect humans, causing the diarrheal and waterborne disease cholera, which is a worldwide health problem. <it>V. cholerae </it>and the free-living amoebae <it>Acanthamoeba </it>species are present in aquatic environments, including drinking water and it has shown that <it>Acanthamoebae </it>support bacterial growth and survival. Recently it has shown that <it>Acanthamoeba </it>species enhanced growth and survival of <it>V. cholerae </it>O1 and O139. Water samples from different cholera endemic areas in Sudan were collected with the aim to detect both <it>V. cholerae </it>and <it>Acanthamoeba </it>species from same natural water samples by polymerase chain reaction (PCR).</p> <p>Findings</p> <p>For the first time both <it>V. cholerae </it>and <it>Acanthamoeba </it>species were detected in same natural water samples collected from different cholera endemic areas in Sudan. 89% of detected <it>V. cholerae </it>was found with <it>Acanthamoeba </it>in same water samples.</p> <p>Conclusions</p> <p>The current findings disclose <it>Acanthamoedae </it>as a biological factor enhancing survival of <it>V. cholerae </it>in nature.</p

Chemical Genetics Reveals Bacterial and Host Cell Functions Critical for Type IV Effector Translocation by Legionella pneumophila

Delivery of effector proteins is a process widely used by bacterial pathogens to subvert host cell functions and cause disease. Effector delivery is achieved by elaborate injection devices and can often be triggered by environmental stimuli. However, effector export by the L. pneumophila Icm/Dot Type IVB secretion system cannot be detected until the bacterium encounters a target host cell. We used chemical genetics, a perturbation strategy that utilizes small molecule inhibitors, to determine the mechanisms critical for L. pneumophila Icm/Dot activity. From a collection of more than 2,500 annotated molecules we identified specific inhibitors of effector translocation. We found that L. pneumophila effector translocation in macrophages requires host cell factors known to be involved in phagocytosis such as phosphoinositide 3-kinases, actin and tubulin. Moreover, we found that L. pneumophila phagocytosis and effector translocation also specifically require the receptor protein tyrosine phosphate phosphatases CD45 and CD148. We further show that phagocytosis is required to trigger effector delivery unless intimate contact between the bacteria and the host is artificially generated. In addition, real-time analysis of effector translocation suggests that effector export is rate-limited by phagocytosis. We propose a model in which L. pneumophila utilizes phagocytosis to initiate an intimate contact event required for the translocation of pre-synthesized effector molecules. We discuss the need for host cell participation in the initial step of the infection and its implications in the L. pneumophila lifestyle. Chemical genetic screening provides a novel approach to probe the host cell functions and factors involved in host–pathogen interactions

Sequencing illustrates the transcriptional response of Legionella pneumophila during infection and identifies seventy novel small non-coding RNAs

Second generation sequencing has prompted a number of groups to re-interrogate the transcriptomes of several bacterial and archaeal species. One of the central findings has been the identification of complex networks of small non-coding RNAs that play central roles in transcriptional regulation in all growth conditions and for the pathogen’s interaction with and survival within host cells. Legionella pneumophila is a Gram-negative facultative intracellular human pathogen with a distinct biphasic lifestyle. One of its primary environmental hosts in the free-living amoeba Acanthamoeba castellanii and its infection by L. pneumophila mimics that seen in human macrophages. Here we present analysis of strand specific sequencing of the transcriptional response of L. pneumophila during exponential and post-exponential broth growth and during the replicative and transmissive phase of infection inside A. castellanii. We extend previous microarray based studies as well as uncovering evidence of a complex regulatory architecture underpinned by numerous non-coding RNAs. Over seventy new non-coding RNAs could be identified; many of them appear to be strain specific and in configurations not previously reported. We discover a family of non-coding RNAs preferentially expressed during infection conditions and identify a second copy of 6S RNA in L. pneumophila. We show that the newly discovered putative 6S RNA as well as a number of other non-coding RNAs show evidence for antisense transcription. The nature and extent of the non-coding RNAs and their expression patterns suggests that these may well play central roles in the regulation of Legionella spp

Reducing the Number of Calibration Surfaces

Calibration charts are used in colour imaging to determine color correction transforms and for spectrally characterising imaging devices. Traditionally, quite complex charts have evolved as it was reasoned that the more reflectances in a chart the more the chart could represent all other reflectances. However, a chart with many reflectances is both expensive, difficult and tedious to use. The difficulty lies in assuming constant lighting conditions over the whole chart and the tedium appears when the chart must be measured using a spectrophotometer. To circumvent these problems researchers have sought methods to find smaller sets of reflectances which, in some sense, represent larger reflectance sets. In this paper we develop an iterative selection procedure where we select individual reflectances from a colour chart. The first is chosen so it best accounts for the majority of the spectral variance. The next best accounts for the variance that is left. In general the ith selected chart reflectance best accounts for the variance among reflectances (given that i ¡ 1 reflectances are already selected). We show that this procedure is weakly optimal and as such compares with prior art which chooses reflectances using simple heuristics. The new method is also much faster than algorithms that are built on stronger optimality conditions. Experiments demonstrate that our new method represents a reasonable compromise between fast (and feasible) reflectance selection and the optimality of the chosen set

Estimating the Bandlimits of an Unknown Sensor

Solving for a camera's sensors based on its response to the surfaces of a calibration target is an ill-conditioned problem with an infi nite number of possible solutions. To obtain a stable estimate we need to control the solution space by constraining the sensors to match some known physical characteristics e. g. sensors are normally constrained to be positive. The use of constraints limits the uncertainty encountered in sensor recovery and results in im-proved estimates. Unfortunately, it is not possible to know which exact constraints should be used in recovering an unknown sensor. In this paper we present a method to estimate the support (the region where the sensor's sensitivity is not zero) of a sensor prior to recovering it. If the sensor's support is limited this constraint is very stringent and imposing it on the solution space results in a clear reduction in the uncertainty encountered in the solution. In the results section we show that it is indeed possible to recover a sensor's bandwidth based on its response to a set of reflectances