Nouvelle approche géologique et géodinamique du Complexe Hydrothermal de Moulay Yacoub, bordure septentrionale du Sillon Sud Rifain

As águas termais de Moulay Yacoub surgem em formações miocénicas do Sulco Sul do Rife. São caracterizadas por forte mineralização, relacionada com a natureza do seu local de armazenamento e circulação em reservatórios de litologias variadas. Apresentam duas fácies químicas principais: uma Cl-Na, pouco diluída, e outra, Cl-Ca-Mg, dominada por águas imaturas. A comparção geoquímica e geotermométrica com outras fontes regionais sugere uma origem mais profunda que o reservatório liássico. A recente descoberta de extrusões de blocos de calcário liássico, de magmatitos paleozóicos, de metassedimentos e de grandes massas de doleritos triássicos, sugere a existência de formações permeáveis sob a cobertura margosa do Miocénico. Os acidentes profundos NE-SW, associados a um cavalgamento cego, sugerem uma relação estreita entre estas águas termais e as extrusões do soco ante-neogénicos. Durante a sua passagem para a superfície, as águas termais de Moulay Yacoub terão sido diluídas através de misturas ocorridas principalmente no reservatório liássico

Nouvelles observations dans le dépocentre volcano-sédimentaire carbonifère du Massif du Tazekka, Moyen-Atlas, Maroc : implications sur l'évolution géodynamique de la chaîne Hercynienne

A análise integrada das estruturas tectónicas e das fácies do Complexo Vulcano Sedimentar do Maciço de Tazekka sugere que este, à escala da grande bacia carbonífera de ante país da Meseta Oriental marroquina, corresponde a um depocentro ou sub bacia em compressão controlada pela propagação, para NW, de dobras de amortecimento do cavalgamento de Hajra Sbaa el Caid. As sequências tectono sedimentares, detrito conglomeráticas e/ou tufíticas, estão associadas a um magmatismo extrusivo com basaltos, andesitos, dacitos, riodacitos e riólitos homogéneos ou piroclásticos com blocos re sedimentados. Estes vulcanitos correspondem a uma sequência sub alcalina equivalente. As sequências calco alcalinas orogénicas características de ambientes de subducção. Estes resultados, assim como a comparação das idades de contracção regional na Meseta marroquina, permitem integrar o Maciço de Tazekka num contexto de wedge top deepzone dum sistema de bacias de ante país flexural, em compressão comandada pela progressão de duas sequências de cavalgamentos prógrados, de NW, desde o Fameno Tournaisiano ao Viseano sup. Terminal Westfaliano inf., da Meseta Oriental para a Meseta Ocidental, em Marrocos setentrional

Hypermethylation-mediated reduction of WWOX expression in intraductal papillary mucinous neoplasms of the pancreas

We have previously shown that WW domain-containing oxidoreductase (WWOX) has tumour-suppressing effects and that its expression is frequently reduced in pancreatic carcinoma. In this study, we examined WWOX expression in intraductal papillary mucinous neoplasm of the pancreas (IPMN) to assess the function of WWOX in pancreatic duct tumourigenesis using immunohistochemistry and methylation-specific polymerase chain reaction analysis. Among 41 IPMNs including intraductal papillary mucinous adenomas (IPMAs) and intraductal papillary mucinous carcinomas (IPMCs), loss or reduced WWOX immunoreactivity was detected in 3 (15%) of 20 IPMAs and 17 (81%) of 21 IPMCs. In addition, hypermethylation of the WWOX regulatory site was detected in 1 (33%) of 3 WWOX(−) IPMAs and 9 (53%) of 17 WWOX(−) IPMCs, suggesting that hypermethylation may possibly be important in the suppression of WWOX expression. Reduction of WWOX expression was significantly correlated with a higher Ki-67 labelling index but was not correlated with the ssDNA apoptotic body index. Interestingly, decreased WWOX expression was significantly correlated with loss of SMAD4 expression in these IPMNs. The results indicate that downregulation of WWOX expression by the WWOX regulatory region hypermethylation is critical for transformation of pancreatic duct

WWOX expression in colorectal cancer—a real-time quantitative RT-PCR study

The WWOX gene is a tumour suppressor gene affected in various types of malignancies. Numerous studies showed either loss or reduction of the WWOX expression in variety of tumours, including breast, ovary, liver, stomach and pancreas. Recent study demonstrated that breast cancer patients exhibiting higher WWOX expression showed significantly longer disease-free survival in contrast to the group with lower relative WWOX level. This work was undertaken to show whether similar phenomena take place in colon tumours and cell lines. To assess the correlation of WWOX gene expression with prognosis and cancer recurrence in 99 colorectal cancer patients, we performed qRT-PCR analysis. We also performed analysis of WWOX promoter methylation status using MethylScreen method and analysis of loss of heterozygosity (LOH) status at two WWOX-related loci, previously shown to be frequently deleted in various types of tumours. A significantly better disease-free survival was observed among patients with tumours exhibiting high level of WWOX (hazard ratio = 0.39; p = 0.0452; Mantel–Cox log-rank test), but in multivariate analysis it was not an independent prognostic factor. We also found that although in colorectal cancer WWOX expression varies among patients and correlates with DFS, the exact mode of decrease in this type of tumour was not found. We failed to find the evidence of LOH in WWOX region, or hypermethylation in promoter regions of this gene. Although we provide the evidence for tumour-suppressive role of WWOX gene expression in colon, we were unable to identify the molecular mechanism responsible for this

ERRα promotes breast cancer cell dissemination to bone by increasing RANK expression in primary breast tumors

Bone is the most common metastatic site for breast cancer. Estrogen-related-receptor alpha (ERRα) has been implicated in cancer cell invasiveness. Here, we established that ERRα promotes spontaneous metastatic dissemination of breast cancer cells from primary mammary tumors to the skeleton. We carried out cohort studies, pharmacological inhibition, gain-of-function analyses in vivo and cellular and molecular studies in vitro to identify new biomarkers in breast cancer metastases. Meta-analysis of human primary breast tumors revealed that high ERRα expression levels were associated with bone but not lung metastases. ERRα expression was also detected in circulating tumor cells from metastatic breast cancer patients. ERRα overexpression in murine 4T1 breast cancer cells promoted spontaneous bone micro-metastases formation when tumor cells were inoculated orthotopically, whereas lung metastases occurred irrespective of ERRα expression level. In vivo, Rank was identified as a target for ERRα. That was confirmed in vitro in Rankl stimulated tumor cell invasion, in mTOR/pS6K phosphorylation, by transactivation assay, ChIP and bioinformatics analyses. Moreover, pharmacological inhibition of ERRα reduced primary tumor growth, bone micro-metastases formation and Rank expression in vitro and in vivo. Transcriptomic studies and meta-analysis confirmed a positive association between metastases and ERRα/RANK in breast cancer patients and also revealed a positive correlation between ERRα and BRCA1mut carriers. Taken together, our results reveal a novel ERRα/RANK axis by which ERRα in primary breast cancer promotes early dissemination of cancer cells to bone. These findings suggest that ERRα may be a useful therapeutic target to prevent bone metastases

Detection and elimination of cellular bottlenecks in protein-producing yeasts

Yeasts are efficient cell factories and are commonly used for the production of recombinant proteins for biopharmaceutical and industrial purposes. For such products high levels of correctly folded proteins are needed, which sometimes requires improvement and engineering of the expression system. The article summarizes major breakthroughs that led to the efficient use of yeasts as production platforms and reviews bottlenecks occurring during protein production. Special focus is given to the metabolic impact of protein production. Furthermore, strategies that were shown to enhance secretion of recombinant proteins in different yeast species are presented