First isolation of two colistin-resistant emerging pathogens, Brevundimonas diminuta and Ochrobactrum anthropi, in a woman with cystic fibrosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Cystic fibrosis afflicted lungs support the growth of many bacteria rarely implicated in other cases of human infections.</p> <p>Case presentation</p> <p>We report the isolation and identification, by 16S rRNA amplification and sequencing, of two emerging pathogens resistant to colistin, <it>Brevundimonas diminuta </it>and <it>Ochrobactrum anthropi</it>, in a 17-year-old woman with cystic fibrosis and pneumonia. The patient eventually responded well to a 2-week regime of imipenem and tobramycin.</p> <p>Conclusion</p> <p>Our results clearly re-emphasize the emergence of new colistin-resistant pathogens in patients with cystic fibrosis.</p

Mycobacterium chimaera pulmonary infection complicating cystic fibrosis: a case report

<p>Abstract</p> <p>Background</p> <p><it>Mycobacterium chimaera </it>is a recently described species within the <it>Mycobacterium avium </it>complex. Its pathogenicity in respiratory tract infection remains disputed. It has never been isolated during cystic fibrosis respiratory tract infection.</p> <p>Case presentation</p> <p>An 11-year-old boy of Asian ethnicity who was born on Réunion Island presented to our hospital with cystic fibrosis after a decline in his respiratory function over the course of seven years. We found that the decline in his respiratory function was correlated with the persistent presence of a <it>Mycobacterium avium </it>complex organism further identified as <it>M. chimaera</it>.</p> <p>Conclusion</p> <p>Using sequencing-based methods of identification, we observed that <it>M. chimaera </it>organisms contributed equally to respiratory tract infections in patients with cystic fibrosis when compared with <it>M. avium </it>subsp. <it>hominissuis </it>isolates. We believe that <it>M. chimaera </it>should be regarded as an emerging opportunistic respiratory pathogen in patients with cystic fibrosis, including young children, and that its detection warrants long-lasting appropriate anti-mycobacterial treatment to eradicate it.</p

Gamma-Ray Emission Concurrent with the Nova in the Symbiotic Binary V407 Cygni

Novae are thermonuclear explosions on a white dwarf surface fueled by mass accreted from a companion star. Current physical models posit that shocked expanding gas from the nova shell can produce X-ray emission but emission at higher energies has not been widely expected. Here, we report the Fermi Large Area Telescope detection of variable gamma-ray (0.1-10 GeV) emission from the recently-detected optical nova of the symbiotic star V407 Cygni. We propose that the material of the nova shell interacts with the dense ambient medium of the red giant primary, and that particles can be accelerated effectively to produce pi0 decay gamma-rays from proton-proton interactions. Emission involving inverse Compton scattering of the red giant radiation is also considered and is not ruled out.Comment: 38 pages, includes Supplementary Online Material; corresponding authors: C.C. Cheung, A.B. Hill, P. Jean, S. Razzaque, K.S. Woo

Molecular Detection of Multiple Emerging Pathogens in Sputa from Cystic Fibrosis Patients

Background: There is strong evidence that culture-based methods detect only a small proportion of bacteria present in the respiratory tracts of cystic fibrosis (CF) patients. Methodology/Principal Findings: Standard microbiological culture and phenotypic identification of bacteria in sputa from CF patients have been compared to molecular methods by the use of 16S rDNA amplification, cloning and sequencing. Twenty-five sputa from CF patients were cultured that yield 33 isolates (13 species) known to be pathogens during CF. For molecular cloning, 760 clones were sequenced (7.263.9 species/sputum), and 53 different bacterial species were identified including 16 species of anaerobes (30%). Discrepancies between culture and molecular data were numerous and demonstrate that accurate identification remains challenging. New or emerging bacteria not or rarely reported in CF patients were detected including Dolosigranulum pigrum, Dialister pneumosintes, and Inquilinus limosus. Conclusions/Significance: Our results demonstrate the complex microbial community in sputa from CF patients, especially anaerobic bacteria that are probably an underestimated cause of CF lung pathology. Metagenomic analysis is urgentl

Inactivation of TIF1γ Cooperates with KrasG12D to Induce Cystic Tumors of the Pancreas

Inactivation of the Transforming Growth Factor Beta (TGFβ) tumor suppressor pathway contributes to the progression of Pancreatic Ductal AdenoCarcinoma (PDAC) since it is inactivated in virtually all cases of this malignancy. Genetic lesions inactivating this pathway contribute to pancreatic tumor progression in mouse models. Transcriptional Intermediary Factor 1 gamma (TIF1γ) has recently been proposed to be involved in TGFβ signaling, functioning as either a positive or negative regulator of the pathway. Here, we addressed the role of TIF1γ in pancreatic carcinogenesis. Using conditional Tif1γ knockout mice (Tif1γlox/lox), we selectively abrogated Tif1γ expression in the pancreas of Pdx1-Cre;Tif1γlox/lox mice. We also generated Pdx1-Cre;LSL-KrasG12D;Tif1γlox/lox mice to address the effect of Tif1γ loss-of-function in precancerous lesions induced by oncogenic KrasG12D. Finally, we analyzed TIF1γ expression in human pancreatic tumors. In our mouse model, we showed that Tif1γ was dispensable for normal pancreatic development but cooperated with Kras activation to induce pancreatic tumors reminiscent of human Intraductal Papillary Mucinous Neoplasms (IPMNs). Interestingly, these cystic lesions resemble those observed in Pdx1-Cre;LSL-KrasG12D;Smad4lox/lox mice described by others. However, distinctive characteristics, such as the systematic presence of endocrine pseudo-islets within the papillary projections, suggest that SMAD4 and TIF1γ don't have strictly redundant functions. Finally, we report that TIF1γ expression is markedly down-regulated in human pancreatic tumors by quantitative RT–PCR and immunohistochemistry supporting the relevance of these findings to human malignancy. This study suggests that TIF1γ is critical for tumor suppression in the pancreas, brings new insight into the genetics of pancreatic cancer, and constitutes a promising model to decipher the respective roles of SMAD4 and TIF1γ in the multifaceted functions of TGFβ in carcinogenesis and development

Design concepts for the Cherenkov Telescope Array CTA: an advanced facility for ground-based high-energy gamma-ray astronomy

Ground-based gamma-ray astronomy has had a major breakthrough with the impressive results obtained using systems of imaging atmospheric Cherenkov telescopes. Ground-based gamma-ray astronomy has a huge potential in astrophysics, particle physics and cosmology. CTA is an international initiative to build the next generation instrument, with a factor of 5-10 improvement in sensitivity in the 100 GeV-10 TeV range and the extension to energies well below 100 GeV and above 100 TeV. CTA will consist of two arrays (one in the north, one in the south) for full sky coverage and will be operated as open observatory. The design of CTA is based on currently available technology. This document reports on the status and presents the major design concepts of CTA

PLoS Pathog

Cytomegalovirus (CMV) is a leading infectious cause of morbidity in immune-compromised patients. γδ T cells have been involved in the response to CMV but their role in protection has not been firmly established and their dependency on other lymphocytes has not been addressed. Using C57BL/6 αβ and/or γδ T cell-deficient mice, we here show that γδ T cells are as competent as αβ T cells to protect mice from CMV-induced death. γδ T cell-mediated protection involved control of viral load and prevented organ damage. γδ T cell recovery by bone marrow transplant or adoptive transfer experiments rescued CD3ε-/- mice from CMV-induced death confirming the protective antiviral role of γδ T cells. As observed in humans, different γδ T cell subsets were induced upon CMV challenge, which differentiated into effector memory cells. This response was observed in the liver and lungs and implicated both CD27+ and CD27- γδ T cells. NK cells were the largely preponderant producers of IFNγ and cytotoxic granules throughout the infection, suggesting that the protective role of γδ T cells did not principally rely on either of these two functions. Finally, γδ T cells were strikingly sufficient to fully protect Rag-/-γc-/- mice from death, demonstrating that they can act in the absence of B and NK cells. Altogether our results uncover an autonomous protective antiviral function of γδ T cells, and open new perspectives for the characterization of a non classical mode of action which should foster the design of new γδ T cell based therapies, especially useful in αβ T cell compromised patients

Gamma-ray emission from internal shocks in novae

Context. Gamma-ray emission at energies ≥100 MeV has been detected from nine novae using the Fermi Large Area Telescope (LAT), and can be explained by particle acceleration at shocks in these systems. Eight out of these nine objects are classical novae in which interaction of the ejecta with a tenuous circumbinary material is not expected to generate detectable gamma-ray emission. Aim. We examine whether particle acceleration at internal shocks can account for the gamma-ray emission from these novae. The shocks result from the interaction of a fast wind radiatively-driven by nuclear burning on the white dwarf with material ejected in the initial runaway stage of the nova outburst. Methods. We present a one-dimensional model for the dynamics of a forward and reverse shock system in a nova ejecta, and for the associated time-dependent particle acceleration and high-energy gamma-ray emission. Non-thermal proton and electron spectra are calculated by solving a time-dependent transport equation for particle injection, acceleration, losses, and escape from the shock region. The predicted emission is compared to LAT observations of V407 Cyg, V1324 Sco, V959 Mon, V339 Del, V1369 Cen, and V5668 Sgr. Results. The ≥100 MeV gamma-ray emission arises predominantly from particles accelerated up to ~100 GeV at the reverse shock and undergoing hadronic interactions in the dense cooling layer downstream of the shock. The emission rises within days after the onset of the wind, quickly reaches a maximum, and its subsequent decrease reflects mostly the time evolution of the wind properties. Comparison to gamma-ray data points to a typical scenario where an ejecta of mass 10−5–10−4 M⊙ expands in a homologous way with a maximum velocity of 1000–2000 km s−1, followed within a day by a wind with a velocity <2000 km s−1 and a mass-loss rate of 10−4–10−3 M⊙ yr−1 declining over a time scale of a few days. Because of the large uncertainties in the measurements, many parameters of the problem are degenerate and/or poorly constrained except for the wind velocity, the relatively low values of which result in the majority of best-fit models having gamma-ray spectra with a high-energy turnover below ~10 GeV. Our typical model is able to account for the main features in the observations of the recent gamma-ray nova ASASSN-16ma. Conclusions. The internal shock model can account for the gamma-ray emission of the novae detected by Fermi LAT. Gamma-ray observations hold potential for probing the mechanism of mass ejection in novae, but should be combined to diagnostics of the thermal emission at lower energies to be more constraining

Microscopic description of proton induced electron emission from insulators: Comparison between alumina and aluminum targets

It is well known that the electron emission yield from insulators is larger than from metals. Most of the previous works on electron emission have been on metals, and very few works have been done on insulators, either experimentally or theoretically. We present in this paper a microscopic description of proton induced electron emission from alumina. Elastic and inelastic interactions for the incident protons and excited electrons are considered as well as the charging-up of the target. The characteristics of proton induced electron emission from alumina (especially the yield γ) are calculated by a Monte Carlo simulation method. A comparison with aluminum targets is done, especially with respect to the influence of the electron inelastic mean free path and of the work function.SCOPUS: ar.jinfo:eu-repo/semantics/publishe