Loss of neutrophil homing to the periodontal tissues modulates the composition and disease potential of the oral microbiota.

Periodontal disease is considered to arise from an imbalance in the interplay between the host and its commensal microbiota, characterized by inflammation, destructive periodontal bone loss and a dysbiotic oral microbial community. The neutrophil is a key component of defence of the periodontium: defects in their number or efficacy of function predisposes individuals to development of periodontal disease. Paradoxically, neutrophil activity, as part of a deregulated inflammatory response, is considered to be an important element in the destructive disease process. In this investigation we examined the role the neutrophil plays in the regulation of the oral microbiota, by analysis of the microbiome composition in mice lacking the CXCR2 neutrophil receptor required for recruitment to the periodontal tissues. A breeding protocol was employed which ensured that only the oral microbiota of wild type (CXCR2+/+) mice was transferred to subsequent generations of wild type, heterozygote and homozygote littermates. In the absence of neutrophils, the microbiome undergoes a significant shift in total load and composition compared to when normal levels of neutrophil recruitment into the gingival tissues occur, and this is accompanied by a significant increase in periodontal bone pathology. However, transfer of the oral microbiome of CXCR2-/- mice into germ free CXCR2+/+ mice led to restoration of the microbiome to the wild type CXCR2+/+ composition and the absence of pathology. These data demonstrate that the composition of the oral microbiome is inherently flexible and is governed to a significant extent by the genetics and resultant phenotype of the host organism

Horizontal and Vertical Transfer of Oral Microbial Dysbiosis and Periodontal Disease

One of the hallmark features of destructive periodontal disease, well documented over the last 50 y, is a change to the quantitative and qualitative composition of the associated microbiology. These alterations are now generally viewed as transformational shifts of the microbial populations associated with health leading to the emergence of bacterial species, which are only present in low abundance in health and a proportionate decrease in the abundance of others. The role of this dysbiosis of the health associated microbiota in the development of disease remains controversial: is this altered microbiology the driving agent of disease or merely a consequence of the altered environmental conditions that invariably accompany destructive disease? In this work, we aimed to address this controversy through controlled transmission experiments in the mouse in which a dysbiotic oral microbiome was transferred either horizontally or vertically into healthy recipient mice. The results of these murine studies demonstrate conclusively that natural transfer of the dysbiotic oral microbiome from a periodontally diseased individual into a healthy individual will lead to establishment of the dysbiotic community in the recipient and concomitant transmission of the disease phenotype. The inherent resilience of the dysbiotic microbial community structure in diseased animals was further demonstrated by analysis of the effects of antibiotic therapy on periodontally diseased mice. Although antibiotic treatment led to a reversal of dysbiosis of the oral microbiome, in terms of both microbial load and community structure, dysbiosis of the microbiome was reestablished following cessation of therapy. Collectively, these data suggest that an oral dysbiotic microbial community structure is stable to transfer and can act in a similar manner to a conventional transmissible infectious disease agent with concomitant effects on pathology. These findings have implications to our understanding of the role of microbial dysbiosis in the development and progression of human periodontal disease

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

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

Comparative Investigation of Ultrafast Excited-State Electron Transfer in Both Polyfluorene-Graphene Carboxylate and Polyfluorene-DCB Interfaces

The Photophysical properties, such as fluorescence quenching, and photoexcitation dynamics of bimolecular non-covalent systems consisting of cationic poly[(9,9-di(3,3&prime;-N,N&prime;-trimethyl-ammonium) propyl fluorenyl-2,7-diyl)-alt-co-(9,9-dioctyl-fluorenyl-2,7-diyl)] diiodide salt (PFN) and anionic graphene carboxylate (GC) have been discovered for the first time via steady-state and time-resolved femtosecond transient absorption (TA) spectroscopy with broadband capabilities. The steady-state fluorescence of PFN is quenched with high efficiency by the GC acceptor. Fluorescence lifetime measurements reveal that the quenching mechanism of PFN by GC is static. Here, the quenching mechanisms are well proven via the TA spectra of PFN/GC systems. For PFN/GC systems, the photo electron transfer (PET) and charge recombination (CR) processes are ultrafast (within a few tens of ps) compared to static interactions, whereas for PFN/1,4-dicyanobenzene DCB systems, the PET takes place in a few hundreds of ps (217.50 ps), suggesting a diffusion-controlled PET process. In the latter case, the PFN+&bull;&ndash;DCB&minus;&bull; radical ion pairs as the result of the PET from the PFN to DCB are clearly resolved, and they are long-lived. The slow CR process (in 30 ns time scales) suggests that PFN+&bull; and DCB&minus;&bull; may already form separated radical ion pairs through the charge separation (CS) process, which recombine back to the initial state with a characteristic time constant of 30 ns. The advantage of the present positively charged polyfluorene used in this work is the control over the electrostatic interactions and electron transfers in non-covalent polyfluorene/quencher systems in DMSO solution

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