Bioremediació bacteriana del mercuri en aigües residuals industrials

Cada vegada augmenta més l'alliberament de mercuri al medi ambient per part de diferents indústries i els mètodes actuals de remediació no són econòmics i/o respectuosos amb l'entorn. Per això la bioremediació s'està imposant cada cop com la millor alternativa. Seguidament s'exposaran diferents tecnologies basades en bioreactors de llit fix amb biofilms bacterians immobilitzats pel tractament d'aigües residuals de la indústria clor-alcalina

Zonation of Ribosomal DNA Transcription Defines a Stem Cell Hierarchy in Colorectal Cancer

Colorectal cancers (CRCs) are composed of an amalgam of cells with distinct genotypes and phenotypes. Here, we reveal a previously unappreciated heterogeneity in the biosynthetic capacities of CRC cells. We discover that the majority of ribosomal DNA transcription and protein synthesis in CRCs occurs in a limited subset of tumor cells that localize in defined niches. The rest of the tumor cells undergo an irreversible loss of their biosynthetic capacities as a consequence of differentiation. Cancer cells within the biosynthetic domains are characterized by elevated levels of the RNA polymerase I subunit A (POLR1A). Genetic ablation of POLR1A-high cell population imposes an irreversible growth arrest on CRCs. We show that elevated biosynthesis defines stemness in both LGR5+ and LGR5− tumor cells. Therefore, a common architecture in CRCs is a simple cell hierarchy based on the differential capacity to transcribe ribosomal DNA and synthesize proteins

Determinació de l’exposició a alcaloides de la pirrolizidina, alumini, aflatoxines i fitosanitaris pel consum de tes i herbes per a infusions a Catalunya: avaluació del risc per a la salut

Alcaloides de la pirrolizidina; Toxines naturals; PlantesAlcaloides de la pirrolizidina; Toxinas naturales; PlantasPyrrolizidine alkaloids; Natural toxins; FloorsEls objectius específics d’aquest estudi són els següents: Determinar i quantificar la presència d’alcaloides de la pirrolizidina, alumini, aflatoxines i fitosanitaris en els tes i les herbes per a infusions del mercat català. Estimar l’exposició dietètica de la població de Catalunya a alcaloides de la pirrolizidina, alumini, aflatoxines i fitosanitaris a través dels tes i herbes per a infusions. Avaluar el risc que representa l’exposició dietètica a aquestes substàncies derivada del consum de tes i herbes per a infusions. Determinar paràmetres microbiològics patògens i indicadors per avaluar l’estat higienicosanitari en els tes i herbes per a infusions

The Nucleolus : a connection between cell fate and tumorigenesis in colorectal cancer

El càncer de colon es caracteritza per presentar una composició cel·lular heterogènia en la qual només un subgrup de cèl·lules retenen la capacitat de contribuir en el manteniment i creixement del tumor. L‘investigació duta a terme en aquesta tesis es focalitza en estudiar aquelles funcions biològiques que estan específicament enriquides en aquesta subpoblació tumoral comparat amb altres cèl·lules cancerígenes que no tenen potencial tumoral. A partir de dades obtingudes en analitzar l’expressió genètica de cèl·lules mare normals i tumorals, hem descobert que l’activitat nucleolar està específicament sobre-activada en aquestes dues poblacions. Hem validat aquestes dades utilitzant diferents models in vivo i in vitro que ens permeten reproduir la biologia intestinal. Hem descobert que l’activitat nucleolar està regulada de forma heterogènia en els tumors de colon. Concretament, són les cèl·lules mare del tumor que presenten una major activació d’aquesta funció biològica. Utilitzant tècniques d’edició del genoma (CRISPR-Cas9) hem pogut generar cèl·lules tumorals de colon que expressen la proteïna RNA Polymerasa I fusionada a una molècula fluorescent (EGFP). D’aquesta manera hem pogut aïllar dels tumors de colon cèl·lules tumorals que presenten una elevada activitat nucleolar. Hem descobert que aquestes cèl·lules tenen una elevada capacitat tumoral, mentre que altres cèl·lules tumorals amb baixa activitat nucleolar no són capaces de retenir aquest potencial cancerigen. Finalment també hem obtingut evidències de que aquesta activitat nucleolar podria estar regulada per la via de senyalització de WNT i que el oncogen MYC podria jugar un paper molt important en aquest escenari. Els resultats obtinguts durant aquesta tesis proveeixen nova informació per al que fa a les funcions biològiques que regulen el potencial tumoral de les cèl·lules de càncer de colon. Això en permetrà entendre millor la malaltia i poder desenvolupar noves teràpies més efectives.Colorectal cancers (CRCs) are amalgams of phenotypically distinct tumor cell populations in which only a subset of cells retain the capacity to sustain tumor growth and propagate the disease. The research in this thesis has focus on the biological functions specifically enriched in this population compared with their differentiated and non-tumorigenic counterparts. Data mining of the expression profiles of normal and cancer stem cells suggested that nucleolar function was enhanced in both types of stem cells. We have validated these in silico observations using different in vitro and in vivo models that allow us to reproduce the intestinal biology and disease. We have discovered that nucleolar activity is heterogeneously regulated in colorectal cancer (CRC) and that high levels of this activity correlate with the undifferentiated state of tumor cells. By means of CRISPR-Cas9 technology we have generated colorectal cancer organoids expressing endogenous RNA Polymerase I (RNA POL I) fused to a EGFP reporter protein. Analysis of tumor cells purified from patient derived xenografts (PDX) expressing high levels of RNA Pol I demonstrated that these cells display elevated rDNA transcriptional activity as well as tumorigenic potential. On the contrary, tumor cells with low levels of RNA Pol I represent a differentiated population with dismal tumor capacity. Furthermore, we also put forward evidence that nucleolar activity is WNT regulated and that the WNT target MYC may be essential in this scenario. Taken together, our data provides new insights on the biology behind the differential tumorigenic behavior and fate of tumor cells in CRCs. Importantly, it also contributes to better understanding cell heterogeneity and may provide the basis for the development of new therapeutic strategies to tackle this disease

The Nucleolus : a connection between cell fate and tumorigenesis in colorectal cancer

El càncer de colon es caracteritza per presentar una composició cel·lular heterogènia en la qual només un subgrup de cèl·lules retenen la capacitat de contribuir en el manteniment i creixement del tumor. L‘investigació duta a terme en aquesta tesis es focalitza en estudiar aquelles funcions biològiques que estan específicament enriquides en aquesta subpoblació tumoral comparat amb altres cèl·lules cancerígenes que no tenen potencial tumoral. A partir de dades obtingudes en analitzar l’expressió genètica de cèl·lules mare normals i tumorals, hem descobert que l’activitat nucleolar està específicament sobre-activada en aquestes dues poblacions. Hem validat aquestes dades utilitzant diferents models in vivo i in vitro que ens permeten reproduir la biologia intestinal. Hem descobert que l’activitat nucleolar està regulada de forma heterogènia en els tumors de colon. Concretament, són les cèl·lules mare del tumor que presenten una major activació d’aquesta funció biològica. Utilitzant tècniques d’edició del genoma (CRISPR-Cas9) hem pogut generar cèl·lules tumorals de colon que expressen la proteïna RNA Polymerasa I fusionada a una molècula fluorescent (EGFP). D’aquesta manera hem pogut aïllar dels tumors de colon cèl·lules tumorals que presenten una elevada activitat nucleolar. Hem descobert que aquestes cèl·lules tenen una elevada capacitat tumoral, mentre que altres cèl·lules tumorals amb baixa activitat nucleolar no són capaces de retenir aquest potencial cancerigen. Finalment també hem obtingut evidències de que aquesta activitat nucleolar podria estar regulada per la via de senyalització de WNT i que el oncogen MYC podria jugar un paper molt important en aquest escenari. Els resultats obtinguts durant aquesta tesis proveeixen nova informació per al que fa a les funcions biològiques que regulen el potencial tumoral de les cèl·lules de càncer de colon. Això en permetrà entendre millor la malaltia i poder desenvolupar noves teràpies més efectives.Colorectal cancers (CRCs) are amalgams of phenotypically distinct tumor cell populations in which only a subset of cells retain the capacity to sustain tumor growth and propagate the disease. The research in this thesis has focus on the biological functions specifically enriched in this population compared with their differentiated and non-tumorigenic counterparts. Data mining of the expression profiles of normal and cancer stem cells suggested that nucleolar function was enhanced in both types of stem cells. We have validated these in silico observations using different in vitro and in vivo models that allow us to reproduce the intestinal biology and disease. We have discovered that nucleolar activity is heterogeneously regulated in colorectal cancer (CRC) and that high levels of this activity correlate with the undifferentiated state of tumor cells. By means of CRISPR-Cas9 technology we have generated colorectal cancer organoids expressing endogenous RNA Polymerase I (RNA POL I) fused to a EGFP reporter protein. Analysis of tumor cells purified from patient derived xenografts (PDX) expressing high levels of RNA Pol I demonstrated that these cells display elevated rDNA transcriptional activity as well as tumorigenic potential. On the contrary, tumor cells with low levels of RNA Pol I represent a differentiated population with dismal tumor capacity. Furthermore, we also put forward evidence that nucleolar activity is WNT regulated and that the WNT target MYC may be essential in this scenario. Taken together, our data provides new insights on the biology behind the differential tumorigenic behavior and fate of tumor cells in CRCs. Importantly, it also contributes to better understanding cell heterogeneity and may provide the basis for the development of new therapeutic strategies to tackle this disease

Weather and gastrointestinal disease in Spain: A retrospective time series regression study

BACKGROUND: A few studies in high-income countries have investigated the relationship between ambient temperature and/or precipitation and the occurrence of gastroenteritis. In most of the cases, hot temperatures and heavy precipitation events have been related to increases in infections. This is of concern as climate change predictions indicate an increase of those extreme events. Our aim was to evaluate the association between meteorological variables and daily gastroenteritis hospitalizations in Spain for the period 1997-2013. METHODS: We obtained data on all hospitalizations which occurred in Spain for the study period from administrative databases and selected those with gastroenteritis as the main diagnosis. Meteorological data was obtained from the European Climate Assessment & Dataset. Daily counts of hospitalizations were linked to meteorological variables in a retrospective ecological time series study using quasi-Poisson regression models with overdispersion and applying the Distributed Lag Non-linear Model (DLNM) framework. RESULTS: Both high and cold temperatures increased the risk of gastroenteritis hospitalizations (relative risk (RR) = 1.21, 95% confidence interval (CI): 1.09, 1.34; and RR = 1.07, 95% CI: 1.00, 1.15, respectively), whereas heavy precipitation was found protective for those hospitalizations (RR = 0.74, 95% CI: 0.63, 0.86). Hot temperatures increased hospitalizations for gastroenteritis classified as foodborne or idiopathic but not those in the group of Others, which were composed mainly of infections by rotavirus and were associated with cold temperatures. CONCLUSIONS: Our findings suggest an important role of ambient temperatures, especially hot temperatures, in increasing gastroenteritis hospitalizations, while the exposure to heavy precipitation events pose opposite and unexpected effects on these infections

Weather and gastrointestinal disease in Spain: A retrospective time series regression study

BACKGROUND: A few studies in high-income countries have investigated the relationship between ambient temperature and/or precipitation and the occurrence of gastroenteritis. In most of the cases, hot temperatures and heavy precipitation events have been related to increases in infections. This is of concern as climate change predictions indicate an increase of those extreme events. Our aim was to evaluate the association between meteorological variables and daily gastroenteritis hospitalizations in Spain for the period 1997-2013. METHODS: We obtained data on all hospitalizations which occurred in Spain for the study period from administrative databases and selected those with gastroenteritis as the main diagnosis. Meteorological data was obtained from the European Climate Assessment & Dataset. Daily counts of hospitalizations were linked to meteorological variables in a retrospective ecological time series study using quasi-Poisson regression models with overdispersion and applying the Distributed Lag Non-linear Model (DLNM) framework. RESULTS: Both high and cold temperatures increased the risk of gastroenteritis hospitalizations (relative risk (RR) = 1.21, 95% confidence interval (CI): 1.09, 1.34; and RR = 1.07, 95% CI: 1.00, 1.15, respectively), whereas heavy precipitation was found protective for those hospitalizations (RR = 0.74, 95% CI: 0.63, 0.86). Hot temperatures increased hospitalizations for gastroenteritis classified as foodborne or idiopathic but not those in the group of Others, which were composed mainly of infections by rotavirus and were associated with cold temperatures. CONCLUSIONS: Our findings suggest an important role of ambient temperatures, especially hot temperatures, in increasing gastroenteritis hospitalizations, while the exposure to heavy precipitation events pose opposite and unexpected effects on these infections

Mex3a marks drug-tolerant persister colorectal cancer cells that mediate relapse after chemotherapy

Colorectal cancer (CRC) patient-derived organoids predict responses to chemotherapy. Here we used them to investigate relapse after treatment. Patient-derived organoids expand from highly proliferative LGR5(+) tumor cells; however, we discovered that lack of optimal growth conditions specifies a latent LGR5(+) cell state. This cell population expressed the gene MEX3A, is chemoresistant and regenerated the organoid culture after treatment. In CRC mouse models, Mex3a(+) cells contributed marginally to metastatic outgrowth; however, after chemotherapy, Mex3a(+) cells produced large cell clones that regenerated the disease. Lineage-tracing analysis showed that persister Mex3a(+) cells downregulate the WNT/stem cell gene program immediately after chemotherapy and adopt a transient state reminiscent to that of YAP(+) fetal intestinal progenitors. In contrast, Mex3a-deficient cells differentiated toward a goblet cell-like phenotype and were unable to resist chemotherapy. Our findings reveal that adaptation of cancer stem cells to suboptimal niche environments protects them from chemotherapy and identify a candidate cell of origin of relapse after treatment in CRC. Batlle and colleagues report that after chemotherapy, Mex3a(+) colorectal cancer cells represent drug-tolerant persister cells that lead to recurrence by downregulating the WNT-Lgr5(+) stem cell program and adopting a transient regenerative state

Stromal gene expression defines poor-prognosis subtypes in colorectal cancer

Recent molecular classifications of colorectal cancer (CRC) based on global gene expression profiles have defined subtypes displaying resistance to therapy and poor prognosis. Upon evaluation of these classification systems, we discovered that their predictive power arises from genes expressed by stromal cells rather than epithelial tumor cells. Bioinformatic and immunohistochemical analyses identify stromal markers that associate robustly with disease relapse across the various classifications. Functional studies indicate that cancer-associated fibroblasts (CAFs) increase the frequency of tumor-initiating cells, an effect that is dramatically enhanced by transforming growth factor (TGF)-β signaling. Likewise, we find that all poor-prognosis CRC subtypes share a gene program induced by TGF-β in tumor stromal cells. Using patient-derived tumor organoids and xenografts, we show that the use of TGF-β signaling inhibitors to block the cross-talk between cancer cells and the microenvironment halts disease progressio