Éditeur(s) : HAL CCSD Society for the Study of Reproduction
Résumé : International audience
Matrix-assisted laser desorption/ionization (MALDI) tissue imaging mass spectrometry is particularly promising among the numerous applications of mass spectrometry. It is used for probing and analyzing the spatial arrangement of a wide range of molecules, including proteins, peptides, lipids, drugs, and metabolites, directly in thin slices of tissue. In the field of proteomics, the technology avoids tedious and time-consuming extraction and fractionation steps classically required for sample analysis. MALDI imaging mass spectrometry is increasingly recognized as a powerful method for clinical proteomics, particularly in cancer research. The technology has particular potential for the discovery of new tissue biomarker candidates, classification of tumors, early diagnosis or prognosis, elucidating pathogenesis pathways, and therapy monitoring. Over recent years, MALDI imaging mass spectrometry has been used for molecular profiling and imaging directly in male and female reproductive tissues. This review will consider some of the recent publications in the field, addressing a range of issues covering embryo development, gene expression product profiling during gametogenesis, and seeking and identifying biomarkers of reproductive cancers. The wealth of advances in mass spectrometry imaging will inevitably attract biologists and clinicians as the advantages and power of this technology become more widely known. This review will also discuss bottlenecks and the many technical issues that remain to be resolved before laboratories in the field can adopt the technology. We foresee that MALDI imaging mass spectrometry will have a major impact in reproductive research by opening new avenues to the understanding of various molecular mechanisms and the diagnosis of reproductive pathologies.
ISSN: 0006-3363

hal-00877851
https://hal.archives-ouvertes.fr/hal-00877851
DOI : 10.1095/biolreprod.111.094896
PUBMED : 22156474

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Iron is an essential micronutrient involved in many biological processes and is often limiting for primary production in large regions of the World Ocean. Metagenomic and physiological studies have identified clades or ecotypes of marine phytoplankton that are specialized in iron depleted ecological niches. Although less studied, eukaryotic picophytoplankton does contribute significantly to primary production and carbon transfer to higher trophic levels. In particular, metagenomic studies of the green picoalga Ostreococcus have revealed the occurrence of two main clades distributed along coast-offshore gradients, suggesting niche partitioning in different nutrient regimes. Here, we present a study of the response to iron limitation of four Ostreococcus strains isolated from contrasted environments. Whereas the strains isolated in nutrient-rich waters showed high iron requirements, the oceanic strains could cope with lower iron concentrations. The RCC802 strain, in particular, was able to maintain high growth rate at low iron levels. Together physiological and transcriptomic data indicate that the competitiveness of RCC802 under iron limitation is related to a lowering of iron needs though a reduction of the photosynthetic machinery and of protein content, rather than to cell size reduction. Our results overall suggest that iron is one of the factors driving the differentiation of physiologically specialized Ostreococcus strains in the ocean.
ISSN: 2045-2322

Droits : http://creativecommons.org/licenses/by/
hal-01502140
http://hal.upmc.fr/hal-01502140
http://hal.upmc.fr/hal-01502140/document
http://hal.upmc.fr/hal-01502140/file/acclimation.pdf
DOI : 10.1038/s41598-017-00216-6

Éditeur(s) : HAL CCSD American Chemical Society
Résumé : International audience
The Chromosome-Centric Human Proteome Project (C-HPP) aims at cataloguing the proteins as gene products encoded by the human genome in a chromosome-centric manner. The existence of products of about 82% of the genes has been confirmed at the protein level. However, the number of so-called "missing proteins" remains significant. It was recently suggested that the expression of proteins that have been systematically missed might be restricted to particular organs or cell types, for example, the testis. Testicular function, and spermatogenesis in particular, is conditioned by the successive activation or repression of thousands of genes and proteins including numerous germ cell- and testis-specific products. Both the testis and postmeiotic germ cells are thus promising sites at which to search for missing proteins, and ejaculated spermatozoa are a potential source of proteins whose expression is restricted to the germ cell lineage. A trans-chromosome-based data analysis was performed to catalog missing proteins in total protein extracts from isolated human spermatozoa. We have identified and manually validated peptide matches to 89 missing proteins in human spermatozoa. In addition, we carefully validated three proteins that were scored as uncertain in the latest neXtProt release (09.19.2014). A focus was then given to the 12 missing proteins encoded on chromosomes 2 and 14, some of which may putatively play roles in ciliation and flagellum mechanistics. The expression pattern of C2orf57 and TEX37 was confirmed in the adult testis by immunohistochemistry. On the basis of transcript expression during human spermatogenesis, we further consider the potential for discovering additional missing proteins in the testicular postmeiotic germ cell lineage and in ejaculated spermatozoa. This project was conducted as part of the C-HPP initiatives on chromosomes 14 (France) and 2 (Switzerland). The mass spectrometry proteomics data have been deposited with the ProteomeXchange Consortium under the data set identifier PXD002367
ISSN: 1535-3893

hal-01187320
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01187320
DOI : 10.1021/acs.jproteome.5b00170
PUBMED : 26168773

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
ISSN: 0305-7453

hal-01470808
https://hal.archives-ouvertes.fr/hal-01470808
DOI : 10.1093/jac/dkw352
PUBMED : 27609051

Éditeur(s) : HAL CCSD American Medical Association (AMA)
Résumé : International audience
IMPORTANCE Although frequently used in treating intensive care unit (ICU) patients with sepsis, empirical antifungal therapy, initiated for suspected fungal infection, has not been shown to improve outcome. OBJECTIVE To determine whether empirical micafungin reduces invasive fungal infection (IFI)-free survival at day 28. DESIGN, SETTING, AND PARTICIPANTS Multicenter double-blind placebo-controlled study of 260 nonneutropenic, nontransplanted, critically ill patients with ICU-acquired sepsis, multiple Candida colonization, multiple organ failure, exposed to broad-spectrum antibacterial agents, and enrolled between July 2012 and February 2015 in 19 French ICUs. INTERVENTIONS Empirical treatment with micafungin (100mg, once daily, for 14 days) (n = 131) vs placebo (n = 129). MAIN OUTCOMES AND MEASURES The primary end pointwas survival without proven IFI 28 days after randomization. Key secondary end points included new proven fungal infections, survival at day 28 and day 90, organ failure, serum (1-3)-beta-D-glucan level evolution, and incidence of ventilator-associated bacterial pneumonia. RESULTS Among 260 patients (mean age 63 years; 91 [35%] women), 251 (128, micafungin group; 123, placebo group) were included in the modified intent-to-treat analysis. Median values were 8 for Sequential Organ Failure Assessment (SOFA) score, 3 for number of Candida-colonized sites, and 99 pg/mL for level of (1-3)-beta-D-glucan. On day 28, there were 82 (68%) patients in the micafungin group vs 79 (60.2%) in the placebo group who were alive and IFI free (hazard ratio [HR], 1.35 [95% CI, 0.87-2.08]). Results were similar among patients with a (1-3)-beta-D-glucan level of greater than 80 pg/mL (n = 175; HR, 1.41 [95% CI, 0.85-2.33]). Day-28 IFI-free survival in patients with a high SOFA score (> 8) was not significantly different when compared between the micafungin vs placebo groups (HR, 1.69 [95% CI, 0.96-2.94]). Use of empirical micafungin decreased the rate of new invasive fungal infection in 4 of 128 patients (3%) in the micafungin group vs placebo (15/123 patients [12%]) (P =.008). CONCLUSIONS AND RELEVANCE Among nonneutropenic critically ill patients with ICU-acquired sepsis, Candida species colonization at multiple sites, and multiple organ failure, empirical treatment with micafungin, compared with placebo, did not increase fungal infection-free survival at day 28.
ISSN: 0098-7484

hal-01405822
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01405822
DOI : 10.1001/jama.2016.14655
PUBMED : 27706483