Down-Regulation of ECRG4, a Candidate Tumor Suppressor Gene, in Human Breast Cancer

INTRODUCTION: ECRG4/C2ORF40 is a potential tumor suppressor gene (TSG) recently identified in esophageal carcinoma. Its expression, gene copy number and prognostic value have never been explored in breast cancer. METHODS: Using DNA microarray and array-based comparative genomic hybridization (aCGH), we examined ECRG4 mRNA expression and copy number alterations in 353 invasive breast cancer samples and normal breast (NB) samples. A meta-analysis was done on a large public retrospective gene expression dataset (n = 1,387) in search of correlations between ECRG4 expression and histo-clinical features including survival. RESULTS: ECRG4 was underexpressed in 94.3% of cancers when compared to NB. aCGH data revealed ECRG4 loss in 18% of tumors, suggesting that DNA loss is not the main mechanism of underexpression. Meta-analysis showed that ECRG4 expression was significantly higher in tumors displaying earlier stage, smaller size, negative axillary lymph node status, lower grade, and normal-like subtype. Higher expression was also associated with disease-free survival (DFS; HR = 0.84 [0.76-0.92], p = 0.0002) and overall survival (OS; HR = 0.72 [0.63-0.83], p = 5.0E-06). In multivariate analysis including the other histo-clinical prognostic features, ECRG4 expression remained the only prognostic factor for DFS and OS. CONCLUSIONS: Our data suggest that ECRG4 is a candidate TSG in breast cancer, the expression of which may help improve the prognostication. If functional analyses confirm this TSG role, restoring ECRG4 expression in the tumor may represent a promising therapeutic approach

Mycophenolic Acid overcomes imatinib and nilotinib resistance of chronic myeloid leukemia cells by apoptosis or a senescent-like cell cycle arrest.

International audienceWe used K562 cells sensitive or generated resistant to imatinib or nilotinib to investigate their response to mycophenolic acid (MPA). MPA induced DNA damage leading to cell death with a minor contribution of apoptosis, as revealed by annexin V labeling (up to 25%). In contrast, cell cycle arrest and positive staining for senescence-associated β-galactosidase activity were detected for a large cell population (80%). MPA-induced cell death was potentialized by the inhibition of autophagy and this is associated to the upregulation of apoptosis. In contrast, senescence was neither decreased nor abrogated in autophagy deficient K562 cells. Primary CD34 cells from CML patients sensitive or resistant to imatinib or nilotinib respond to MPA although apoptosis is mainly detected. These results show that MPA is an interesting tool to overcome resistance in vitro and in vivo mainly in the evolved phase of the disease

Managing banana genetic resources and genomic information with the Triplet Drupal/Tripal/Chado [P0944]

Unraveling the genetic diversity held in genebanks on a large scale is underway, given the advances in NGS-based technologies that produce high-density genetic markers for a large number of samples at low cost. As SNP markers are being mapped on the reference genomes, it is important to develop interoperable system for managing both genomic data and genetic resources. The latter are often managed through bespoke information systems. The Musa Germplasm Information System (MGIS), the main banana genetic resource website, has recently been developed to address those needs in a convenient and flexible way. First of all, we decided to head for a generic database schema, such as CHADO, and to use a robust content management system such as Drupal as the web interface. The Tripal module provides the "glue" between these two parts and drastically reduces development time. Using this trio, we were able to quickly recreate in few months a complete and scalable site and expand it with new features. We now have a germplasm management system allowing collection browsing, and accession browsing, searching and ordering. Accession passport data have been enriched by geographical data, phenotyping characterization data, and information from diversity studies based on molecular markers and SNPs. As a first-use case, such genotyping studies allow linking with the Banana Genome Hub (BGH) website to explore these data in the genome context. (Texte intégral

Using satellite estimates of aboveground biomass to assess carbon stocks in a mixed-management, semi-deciduous tropical forest in the Yucatan Peninsula

Information on the spatial distribution of forest aboveground biomass (AGB) and its uncertainty is important to evaluate management and conservation policies in tropical forests. However, the scarcity of field data and robust protocols to propagate uncertainty prevent a robust estimation through remote sensing. We upscaled AGB from field data to LiDAR, and to landscape scale using Sentinel-2 and ALOS-PALSAR through machine learning, propagated uncertainty using a Monte Carlo framework and explored the relative contributions of each sensor. Sentinel-2 outperformed ALOS-PALSAR (R2 = 0.66, vs 0.50), however, the combination provided the best fit (R2 = 0.70). The combined model explained 49% of the variation comparing against plots within the calibration area, and 17% outside, however, 94% of observations outside calibration area fell within the 95% confidence intervals. Finally, we partitioned the distribution of AGB in different management and conservation categories for evaluating the potential of different strategies for conserving carbon stock

Vector-Borne Diseases and Climate Change in the Environmental Context in Haiti

Climate change is one of the main challenges facing many countries, particularly developing countries, because of its negative impact on their various ecosystems and their socio-economic development, which very often leads them down a slow descent into poverty. This is because climate change can manifest itself in different forms such as climate variability and extreme events (droughts, epidemics, floods, storms and hurricanes), which can affect biodiversity and cause many human and animal diseases and deaths. In fact, the evolution of ecosystems is dependent on climate and environmental change and appears to be closely associated with many emerging or re-emerging diseases. In general, the ecosystems considered to be most exposed to climate change are those located in and around the intertropical convergence zone in particular. They are believed to be closely linked to the occurrence of several emerging diseases, particularly vector-borne diseases. For years, the Republic of Haiti has been experiencing the adverse effects of these global changes with a marked disruption of its rainfall pattern and prolonged periods of drought as well as a pronounced increase in temperatures even in high altitude areas. Although there is evidence that climate change is increasing the frequency of vector-borne diseases and may contribute to increasing the virulence of their pathogens, there are very few studies conducted in Haiti on the relationship between climate change and vector-borne diseases. The purpose of this chapter is to define the interrelationships between climate change and vector-borne diseases in Haiti by identifying avenues of research to better understand the effects of climate change on public health and to make appropriate recommendations to decision-makers to ensure proper management

The potential distribution of Bactrocera dorsalis: Considering phenology and irrigation patterns

A species in the Bactrocera dorsalis (Hendel) complex was detected in Kenya during 2003 and classified as Bactrocera invadens Drew, Tsuruta & White. Having spread rapidly throughout Africa, it threatens agriculture due to crop damage and loss of market access. In a recent revision of the B. dorsalis complex, B. invadens was incorporated into the species B. dorsalis. The potential distribution of B. dorsalis has been previously modelled. However, previous models were based on presence data and did not incorporate information on the seasonal phenology of B. dorsalis, nor on the possible influence that irrigation may have on its distribution. Methyl eugenol-baited traps were used to collect B. dorsalis in Africa. Seasonal phenology data, measured as fly abundance throughout the year, was related to each location's climate to infer climatic growth response parameters. These functions were used along with African distribution records and development studies to fit the niche model for B. dorsalis, using independent global distribution records outside Africa for model validation. Areas at greatest risk of invasion by B. dorsalis are South and Central America, Mexico, southernmost USA, parts of the Mediterranean coast, parts of Southern and Eastern Australia and New Zealand's North Island. Under irrigation, most of Africa and Australia appear climatically suitable. (Résumé d'auteur

Annual population dynamics of mango fruit flies (Diptera: Tephritidae) in West Africa: Socio-economic aspects, host phenology and implications for management

Losses in West African commercial mango orchards due to fruit fly infestations have exceeded 50% by the middle of the crop season since 2005, resulting in considerable income loss for the growers. Materials and methods. In 2009, weekly monitoring of adult fruit fly species of economic significance was carried out in eight West African countries at 12 sites across five agro-ecological zones: (i) Humid Forest, (ii) Guinean savanna, (iii) Southern Sudan, (iv) Northern Sudan, and (v) Sahelian. Trapping was performed using methyl eugenol and terpinyl acetate in 288 Tephritraps, targeting Bactrocera invadens and Ceratitis cosyra. Results. The data showed that B. Invadens was present throughout the year in the Forest zone, abundant for 7 months, with a peak in May at the end of the mango season, C. cosyra being totally absent. In the Guinean savanna zone, B. invadens was abundant for 6-7 months, with a peak at the beginning of June coinciding with the season, with a few C. cosyra. In the Southern Sudan zone, B. invadens was abundant for 6 months, with a peak in mid-June during the season, C. cosyra peaking in April. In the Northern Sudan zone, B. invadens was abundant for 5 months, with a peak at the end of June at the end of the season, C. cosyra peaking in May. In the Sahelian zone, B. invadens was abundant for 4 months, peaking in August during the sea-son, C. cosyra peaking just before. These preliminary results showed that the exotic species, B. invadens, was present at high levels [mean peak of 378 flies per trap per day (FTD)] in all agro-eco-logical zones, while the native species, C. cosyra, preferred the drier zones of West Africa, with lower population levels (mean peak of 77 FTD).Conclusion. Detection trapping of male flies with parapheromones is a useful indicator of field population levels and could be used to deploy control measures (IPM package) in a timely manner when the Economic Injury Level is reached. Control strategies for these quarantine mango fruit fly species are discussed with respect to agro-ecological zones and the phenological stages of the mango tree. (Résumé d'auteur

The Expression of Myeloproliferative Neoplasm-Associated Calreticulin Variants Depends on the Functionality of ER-Associated Degradation

BACKGROUND: Mutations in CALR observed in myeloproliferative neoplasms (MPN) were recently shown to be pathogenic via their interaction with MPL and the subsequent activation of the Janus Kinase - Signal Transducer and Activator of Transcription (JAK-STAT) pathway. However, little is known on the impact of those variant CALR proteins on endoplasmic reticulum (ER) homeostasis. METHODS: The impact of the expression of Wild Type (WT) or mutant CALR on ER homeostasis was assessed by quantifying the expression level of Unfolded Protein Response (UPR) target genes, splicing of X-box Binding Protein 1 (XBP1), and the expression level of endogenous lectins. Pharmacological and molecular (siRNA) screens were used to identify mechanisms involved in CALR mutant proteins degradation. Coimmunoprecipitations were performed to define more precisely actors involved in CALR proteins disposal. RESULTS: We showed that the expression of CALR mutants alters neither ER homeostasis nor the sensitivity of hematopoietic cells towards ER stress-induced apoptosis. In contrast, the expression of CALR variants is generally low because of a combination of secretion and protein degradation mechanisms mostly mediated through the ER-Associated Degradation (ERAD)-proteasome pathway. Moreover, we identified a specific ERAD network involved in the degradation of CALR variants. CONCLUSIONS: We propose that this ERAD network could be considered as a potential therapeutic target for selectively inhibiting CALR mutant-dependent proliferation associated with MPN, and therefore attenuate the associated pathogenic outcomes