116 research outputs found
Interbacterial Competition in the Burkholderia cepacia Complex
No full textBacteria often live in multicellular communities composed of multiple species. Bacteria interact with one another during intimate cell-cell contact within such environments, and these interactions influence the ecology and evolution of multicellular communities. Polymicrobial communities reside within the respiratory tracts of individuals with the genetic disorder cystic fibrosis (CF). Polymicrobial respiratory infections are characteristic of CF disease, and canonical pathogens can dominate the airway communities during infections. Intriguingly, pathogenic species of the Burkholderia cepacia complex (Bcc) can establish infections within polymicrobial CF respiratory tracts, even those dominated by the prevalent pathogen Pseudomonas aeruginosa, though these infections do not occur in young individuals and are limited to teenage and adult CF patients. Here we describe two mechanisms of cell contact-dependent interbacterial competition that provide Bcc pathogens ecological advantages: contact-dependent growth inhibition (CDI) and the type VI secretion system (T6SS). We show the Bcc CF pathogen Burkholderia dolosa produces three CDI systems that facilitate killing of competitor cells during co-culture experiments. These systems deliver unique polymorphic toxins to target cells, and production of immunity proteins cognate to these toxins rescues target cells from killing. We show the genes encoding one B. dolosa CDI system are present in multiple sequenced Bcc strains, suggesting this mechanism of interbacterial competition may be prevalent among Bcc pathogens. Using the Bcc pathogen Burkholderia cenocepacia, we show that the T6SS of Bcc species mediates strong competition against a variety of target bacteria. We describe the striking ability for this pathogen to use its T6SS to outcompete P. aeruginosa isolates from teenage and adult CF patients, but not P. aeruginosa isolates from young patients. Whole genome sequencing identified mutations in the susceptible P. aeruginosa isolates that abrogate activity by their own T6SSs, thus inhibiting their retaliation to attack from B. cenocepacia and promoting their elimination from co-cultures. These competitive dynamics may explain why Bcc infections are limited to teenage and adult CF patients. Altogether CDI and T6S likely provide Bcc pathogens competitive advantages within the polymicrobial communities of the CF respiratory tract, promoting their colonization and infection potential, and thus may be attractive targets for therapies treating these infections.Doctor of Philosoph
Hyperthermie des neuroleptiques secondaires à un antiémétique administré par voie orale: le métopimazine
No full textAn Analysis of Genetic Variation and Population Structure in the Least (Eutamias minimus) and Uinta (E. imbrinus) Chipmunks
No full textAβ modulates PKR, MTOR/4EBP1 and P70S6K signaling controls of translation in neural cells
No full textFund Clin Pharmacol
No full textDespite being a standard of care in B-cell
malignancies, a benefit–risk assessment in real-life set-
tings of ibrutinib, the first-in-class Bruton tyrosine
kinase (BTK) inhibitor, was still needed. This work
aimed to provide real-life data on patterns of use and
safety of ibrutinib through two data sources, VigiBase®
and SNDS. Firstly, co-administration of ibrutinib and
anticoagulants was associated with a 2.5-fold
increased risk of clinically relevant bleeding, without
any difference between vitamin K antagonists and
direct oral anticoagulants. Secondly, 1-year incidence
of fungal invasive infections was 1.3% in ibrutinib-
treated patients, with the following predictive factors:
stem cell transplantation, neutropenia, corticosteroids,
and chronic respiratory diseases, previous treatment
and combination with anti-CD20 agents. Lastly, rele-
vant safety signals emerged from VigiBase®, mainly
cardiovascular and ocular reactions. Taken together,
these findings contributed to providing essential
information about monitoring and management of
ibrutinib-treated patients and crucial insights for real-
world surveillance of next-generation BTK inhibitor
Data from: Rearing and sampling methods for estimating spruce budworm development rates at constant temperatures
No full textWe describe an experimental protocol for measuring the response of spruce budworm post-diapause larval development to temperature. This protocol is specifically designed to include measurements of development near their upper and lower thermal thresholds. The application of this protocol to a laboratory colony allowed for the first experimental evidence that spruce budworm larval development occurs at temperatures as low as 5 ºC and as high as 35 ºC and provides data to estimate development rates at temperatures from 5–35 ºC in 5 ºC increments. Our protocol is also designed to minimize mortality near the thermal development thresholds thus allowing for multi-generational studies. We observed developmental plasticity in larvae reared at constant temperatures, particularly the occurrence of up to 42% of some individuals requiring only five instars to complete development, compared to the expected six instars. An occurrence that exhibited no clear relation to temperature. While this protocol is specifically designed for spruce budworm, it provides a template for the study of other species' developmental responses to temperature.Data and code are provided to replicate the analysis of head capsule widths and the fitting of the Dyer's law relationshop. Data and code are also given to reproduce all Figures except 2 & 5.Data collected from rearing of spruce budworm larvae at controlled temperatures in a laboratory. Methodological details are provided in the associated manuscript and readme file
First ISOCAM Images of the Milky Way
No full textISOGAL is a 15μm ISOCAM survey of ~12deg^2^ in the Galactic Plane interior to |l|=45°. In combination with IJK data from the near-infrared southern sky survey DENIS, the ISO images allow the first detailed study of stellar populations throughout the inner Galaxy. We present preliminary results from a test observation at l= -45° with 6" pixels and completeness limit 8mJy. Of the ~3000 sources deg^-2^ detected, about half are KM giants, seen through extinction of up to A_v_~30, while most of the remainder are probably dusty young stars. Although away from bright IRAS regions, the field displays spectacular emission features, and, unexpectedly, a number of regions which are optically thick at 15μm. The dark regions are presumably dense filaments with A_v_>25
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