2,817 research outputs found
Candida albicans Inhibits Pseudomonas aeruginosa Virulence through Suppression of Pyochelin and Pyoverdine Biosynthesis.
Bacterial-fungal interactions have important physiologic and medical ramifications, but the mechanisms of these interactions are poorly understood. The gut is host to trillions of microorganisms, and bacterial-fungal interactions are likely to be important. Using a neutropenic mouse model of microbial gastrointestinal colonization and dissemination, we show that the fungus Candida albicans inhibits the virulence of the bacterium Pseudomonas aeruginosa by inhibiting P. aeruginosa pyochelin and pyoverdine gene expression, which plays a critical role in iron acquisition and virulence. Accordingly, deletion of both P. aeruginosa pyochelin and pyoverdine genes attenuates P. aeruginosa virulence. Heat-killed C. albicans has no effect on P. aeruginosa, whereas C. albicans secreted proteins directly suppress P. aeruginosa pyoverdine and pyochelin expression and inhibit P. aeruginosa virulence in mice. Interestingly, suppression or deletion of pyochelin and pyoverdine genes has no effect on P. aeruginosa's ability to colonize the GI tract but does decrease P. aeruginosa's cytotoxic effect on cultured colonocytes. Finally, oral iron supplementation restores P. aeruginosa virulence in P. aeruginosa and C. albicans colonized mice. Together, our findings provide insight into how a bacterial-fungal interaction can modulate bacterial virulence in the intestine. Previously described bacterial-fungal antagonistic interactions have focused on growth inhibition or colonization inhibition/modulation, yet here we describe a novel observation of fungal-inhibition of bacterial effectors critical for virulence but not important for colonization. These findings validate the use of a mammalian model system to explore the complexities of polymicrobial, polykingdom infections in order to identify new therapeutic targets for preventing microbial disease
Yeasts isolated from different European dry-sausages in the course of ripening
The evolution in counts of yeasts from six lots of different dry-sausages produced in three European Union (EU) countries (France, Italy and Spain) is tested. Each lot was analyzed in three phases of their production: fresh product, first staged drying and final product. Three samples were analyzed in each test. Counts of yeasts during the ripening process showed an irregular evolution. Regarding the species isolated, the most frequent ones belonged to genera Candida (C. albicans, C. famata, C. guillermondii, C. krusei, C. parapsilosis, C. stellatoidea, C. zeylanoides.), Trichosporon (T. capitatum, T. beigelli), Rhodotorula and Geotrichum (G. candidum)
From the oceans to the cloud: Opportunities and challenges for data, models, computation and workflows.
© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Vance, T. C., Wengren, M., Burger, E., Hernandez, D., Kearns, T., Medina-Lopez, E., Merati, N., O'Brien, K., O'Neil, J., Potemrag, J. T., Signell, R. P., & Wilcox, K. From the oceans to the cloud: Opportunities and challenges for data, models, computation and workflows. Frontiers in Marine Science, 6(211), (2019), doi:10.3389/fmars.2019.00211.Advances in ocean observations and models mean increasing flows of data. Integrating observations between disciplines over spatial scales from regional to global presents challenges. Running ocean models and managing the results is computationally demanding. The rise of cloud computing presents an opportunity to rethink traditional approaches. This includes developing shared data processing workflows utilizing common, adaptable software to handle data ingest and storage, and an associated framework to manage and execute downstream modeling. Working in the cloud presents challenges: migration of legacy technologies and processes, cloud-to-cloud interoperability, and the translation of legislative and bureaucratic requirements for “on-premises” systems to the cloud. To respond to the scientific and societal needs of a fit-for-purpose ocean observing system, and to maximize the benefits of more integrated observing, research on utilizing cloud infrastructures for sharing data and models is underway. Cloud platforms and the services/APIs they provide offer new ways for scientists to observe and predict the ocean’s state. High-performance mass storage of observational data, coupled with on-demand computing to run model simulations in close proximity to the data, tools to manage workflows, and a framework to share and collaborate, enables a more flexible and adaptable observation and prediction computing architecture. Model outputs are stored in the cloud and researchers either download subsets for their interest/area or feed them into their own simulations without leaving the cloud. Expanded storage and computing capabilities make it easier to create, analyze, and distribute products derived from long-term datasets. In this paper, we provide an introduction to cloud computing, describe current uses of the cloud for management and analysis of observational data and model results, and describe workflows for running models and streaming observational data. We discuss topics that must be considered when moving to the cloud: costs, security, and organizational limitations on cloud use. Future uses of the cloud via computational sandboxes and the practicalities and considerations of using the cloud to archive data are explored. We also consider the ways in which the human elements of ocean observations are changing – the rise of a generation of researchers whose observations are likely to be made remotely rather than hands on – and how their expectations and needs drive research towards the cloud. In conclusion, visions of a future where cloud computing is ubiquitous are discussed.This is PMEL contribution 4873
ExoMars Raman Laser Spectrometer RLS, a tool for the potential recognition of wet target craters on Mars
In the present work, NIR, LIBS, Raman and XRD techniques have been
complementarily used to carry out a comprehensive characterization of a
terrestrial analogue selected from the Chesapeake Bay Impact Structure (CBIS).
The obtained data clearly highlight the key role of Raman spectroscopy in the
detection of minor and trace compounds, through which inferences about
geological processes occurred in the CBIS can be extrapolated. Beside the use
of commercial systems, further Raman analyses were performed by the Raman Laser
Spectrometer (RLS) ExoMars Simulator. This instrument represents the most
reliable tool to effectively predict the scientific capabilities of the
ExoMars/Raman system that will be deployed on Mars in 2021. By emulating the
analytical procedures and operational restrictions established by the ExoMars
mission rover design, it was proved that the RLS ExoMars Simulator is able to
detect the amorphization of quartz, which constitutes an analytical clue of the
impact origin of craters. On the other hand, the detection of barite and
siderite, compounds crystallizing under hydrothermal conditions, helps to
indirectly confirm the presence of water in impact targets. Furthermore, the
RLS ExoMars Simulator capability of performing smart molecular mappings was
also evaluated. According to the obtained results, the algorithms developed for
its operation provide a great analytical advantage over most of the automatic
analysis systems employed by commercial Raman instruments, encouraging its
application for many additional scientific and commercial purposes
SpeS: A Novel Superantigen and Its Potential as a Vaccine Adjuvant against Strangles.
Bacterial superantigens (sAgs) are powerful activators of the immune response that trigger unspecific T cell responses accompanied by the release of proinflammatory cytokines. Streptococcus equi (S. equi) and Streptococcus zooepidemicus (S. zooepidemicus) produce sAgs that play an important role in their ability to cause disease. Strangles, caused by S. equi, is one of the most common infectious diseases of horses worldwide. Here, we report the identification of a new sAg of S. zooepidemicus, SpeS, and show that mutation of the putative T cell receptor (TCR)-binding motif (YAY to IAY) abrogated TCR-binding, whilst maintaining interaction with major histocompatibility complex (MHC) class II molecules. The fusion of SpeS and SpeSY39I to six S. equi surface proteins using two different peptide linkers was conducted to determine if MHC class II-binding properties were maintained. Proliferation assays, qPCR and flow cytometry analysis showed that SpeSY39I and its fusion proteins induced less mitogenic activity and interferon gamma expression when compared to SpeS, whilst retaining Antigen-Presenting Cell (APC)-binding properties. Our data suggest that SpeSY39I-surface protein fusions could be used to direct vaccine antigens towards antigen-presenting cells in vivo with the potential to enhance antigen presentation and improve immune responses
Assessing matrilineal genetic diversity in Mexico through the analysis of ancient mitogenomes spanning 2,300-500 YBP
EP05.02-003 Durvalumab after Chemoradiotherapy (CRT) in Unresectable Stage III NSCLC. Comparative Study of Two Cohorts in the Real-World Setting
[EN] Introduction: Durvalumab is the new standard of care for unresectable
locally advanced NSCLC, with PD-L1 _1% and who did not
have progression after CRT treatment in the European Union. Our
study compares the effectiveness and the frequency of radiation
pneumonitis in patients treated with concurrent CRT with or without
durvalumab consolidation during the same period in real clinical
practice. Methods: A single-center retrospective study. 71 treated
patients with unresectable stage III NSCLC were included between
March 2018 and December 2021, 37 with CRT followed by durvalumab
and 34 with CRT alone. Real-world progression-free survival
(rwPFS) and real-world overall survival (rwOS) were calculated since
the date of the end CRT. Propensity score matching (PSM) 1:1 was
used to account for differences in baseline characteristics. Results:
Median age was 67 years (range 46-82). 25.4% of the patients were
_75 years old. 78.9% were men and 53.5% former smokers. 54.9%
had squamous histology and 28%, 51% and 21% stage IIIA, IIIB and
IIIC disease, respectively. The most used scheme was carboplatinpaclitaxel
(43.7%), receiving induction chemotherapy in up to 54.9%
of patients. 73.2% received between 60-66 Gy doses of radiotherapy.
Median time from end of CRT to onset durvalumab was 44 days
(range 13-120) with a median of 14 infusions (range 6-27). Of the
34 patients without durvalumab treatment, the expression PD-L1
<1% (58.8%) was the most frequent cause for rejecting consolidation
therapy. After PSM analysis, patients distributions were well
balanced. With a median follow-up of 19.7 months (range 1.4-36.6);
median rw-PFS was 9.3 months (95% CI, 5-13.5) without durvalumab
and 17 months (95% CI, 11-22.9) with durvalumab (p¼0.013).
Median rw-OS was 19.3 months (95% CI, 3.8-34.8) without durvalumab
and 29.9 months (95% CI, 23.3-36.6) with durvalumab
(p¼0.241) with a rw-OS% at 6, 18 and 24 months of 90%, 62% and
49% vs 100%, 86% and 74%, respectively. The rate of radiation
pneumonitis was more frequent with durvalumab consolidation
(56.8% against 44.1%), (p¼0.346), especially within 3 months after
CRT. G3 pneumonitis was only observed in the consolidation therapy.
Conclusions: Our results demonstrate the effectiveness of
durvalumab consolidation after CRT in real-world patients with
unresectable stage III NSCLC. Further sample and longer follow-up
are required to obtain more accurate results. Active surveillance and
appropriate management for radiation pneumonitis are needed, in
especially in candidates for consolidation treatmentS
EP05.02-002 Who Benefits More of Durvalumab after Chemoradiotherapy (CRT) in Real-World Patients with Locally Advanced Non-Small-Cell Lung Cancer (NSCLC)?
[EN] Introduction: Durvalumab received EMA approval as consolidation
therapy (CT) for unresectable stage III NSCLC with PD-L1 _1% and
who did not have progression after CRT. Our objective was to analyze
in real clinical practice the effectiveness of durvalumab and explore the
clinical factors that may be associated with the benefit from CT.
Methods: Retrospective study was made at Hospital of Leon (Spain),
including 37 patients with locally advanced NSCLC treated with durvalumab
after CRT treatment between March 2018 and october 2021
(40.5% patients were included in the durvalumab early access program).
The neutrophil-to-lymphocyte ratio (NLR) could identified after
CRT as a factor that may be benefit from durvalumab. Results: Median
age was 67 years (range 46-82 years). 40.5% of patients were _70
years old. 78.4% were male and 51.4% smokers. 54% had non-squamous
histology. PD-L1 expression was <1% in 5% and not available in
8% patients. 2.7% ROS1 rearrangements, 5.4% KRAS mutations and
not available in 43.2% patients. Stage IIIA, IIIB, IIIC disease were
24.3%, 54.1% and 21.6%, respectively. Median time from end of CRT to
onset durvalumab was 44 days (range 13-120 days). Overall median CT
duration was 214.8 days (range 69-399 days) with a median of 14
infusions (range 6-27 infusions). With a median follow up of 19.7
months (range 1.4-34.9 months); 67.6% had stopped CT: 37.8% due to
completing treatment, 16.2% disease progression, 10.8% adverse event
and 2.7% due to COVID19 infection. Median real-world progressionfree
survival (rwPFS) was 17 months (95% CI, 11-23). Median realworld
overall survival (rwOS) was 29.9 months (95% CI, 23.3-36.6). %
rwOS at 6, 18 and 24 months were 100%, 86.9% and 74.5%, respectively.
For patients with post-CRT NLR not exceeding the cohort median
value of 6, receipt of durvalumab was associated with an improvement
in rwOS (median not reached vs 25.7 months; p¼0.025). 56.8% patients
had any grade of radiation pneumonitis (median time from CRT
start: 119 days [range 36-241 days]). Of these, 19% patients developed
worsening of radiation pneumonitis with durvalumab. 54,1% developed
immune-mediated toxicity, mostly G1-2 (85.1%). Conclusions:
Our results demonstrate the effectiveness of durvalumab consolidation
in this patients population in a real-life setting. We identified low NLR
after CRT as a potentially predictive factor for the benefit of CT in
locally advanced NSCLC.S
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