Time-resolved Fourier transform infrared emission spectroscopy of CO ∆v = 1 and ∆v = 2 extended bands in the ground X1Σ+ state produced by formamide glow discharge

This paper presents an extension to our knowledge of ∆v = 1 and ∆v = 2 bands of carbon monoxide in the ground state, measured by Fourier transform infrared spectroscopy of glow discharge of formamide-nitrogen mixture. Lines in declared bands are measured up to v = 30 for ∆v = 1 and up to v = 24 for ∆v = 2 band, by use of both InSb and MCT detectors, which have not been measured in the laboratory before. Dunham parameters obtained by fitting our lines are presented as well as comparison to other authors. The paper also demonstrates the interesting impossibility of sufficient population of ∆v = 2 band of CO when only pure CO is used in the glow discharge, instead of formamide-based mixture. Additionally, we present a non-LTE model to describe the intensity pattern of the ∆v = 1 and the ∆v = 2 bands of 12C16O experimental spectra by simulating the corresponding non-LTE vibrational populations of CO

EU Agro Biogas Project

EU-AGRO-BIOGAS is a European Biogas initiative to improve the yield of agricultural biogas plants in Europe, to optimise biogas technology and processes and to improve the efficiency in all parts of the production chain from feedstock to biogas utilisation. Leading European research institutions and universities are cooperating with key industry partners in order to work towards a sustainable Europe. Fourteen partners from eight European countries are involved. EU-AGRO-BIOGAS aims at the development and optimisation of the entire value chain – to range from the production of raw materials, the production and refining of biogas to the utilisation of heat and electricity

The hypoxia-inducible genes VEGF and CA9 are differentially regulated in superficial vs invasive bladder cancer

Regulation by hypoxia may underlie the expression of vascular endothelial growth factor in bladder cancer. We have compared the distribution of vascular endothelial growth factor mRNA with a hypoxia marker, carbonic anhydrase 9 (CA IX). vascular endothelial growth factor mRNA was analysed by in situ hybridisation and CA IX by immunochemistry in 22 cases of bladder cancer. The relationship of microvessels to the distribution of CA IX was determined. In a separate series of 49 superficial tumours, CA IX immunostaining was compared with clinico-pathological outcome. In superficial and invasive disease there was overlap in the expression of vascular endothelial growth factor and CA IX, CA IX being more widespread. Both were expressed predominantly on the luminal surface, and surrounding areas of necrosis (invasive tumours). Expression of both factors was greater in superficial disease. Expression was absent within ∼80 μm of microvessels. Unlike vascular endothelial growth factor, CA IX did not predict outcome in superficial disease. Differential responses to reoxygenation provide one explanation: vascular endothelial growth factor mRNA declined rapidly, while CA IX expression was sustained for >72 h. Expression of vascular endothelial growth factor mRNA in bladder tumours is consistent with hypoxic regulation and suggests differential regulation in superficial vs invasive disease. The expression of CA IX on the luminal surface justifies investigation of its utility as a therapeutic target/prognostic indicator

Ariel – a window to the origin of life on early earth?

Is there life beyond Earth? An ideal research program would first ascertain how life on Earth began and then use this as a blueprint for its existence elsewhere. But the origin of life on Earth is still not understood, what then could be the way forward? Upcoming observations of terrestrial exoplanets provide a unique opportunity for answering this fundamental question through the study of other planetary systems. If we are able to see how physical and chemical environments similar to the early Earth evolve we open a window into our own Hadean eon, despite all information from this time being long lost from our planet’s geological record. A careful investigation of the chemistry expected on young exoplanets is therefore necessary, and the preparation of reference materials for spectroscopic observations is of paramount importance. In particular, the deduction of chemical markers identifying specific processes and features in exoplanetary environments, ideally “uniquely”. For instance, prebiotic feedstock molecules, in the form of aerosols and vapours, could be observed in transmission spectra in the near future whilst their surface deposits could be observed from reflectance spectra. The same detection methods also promise to identify particular intermediates of chemical and physical processes known to be prebiotically plausible. Is Ariel truly able to open a window to the past and answer questions concerning the origin of life on our planet and the universe? In this paper, we discuss aspects of prebiotic chemistry that will help in formulating future observational and data interpretation strategies for the Ariel mission. This paper is intended to open a discussion and motivate future detailed laboratory studies of prebiotic processes on young exoplanets and their chemical signatures

Alternative splicing variant of the hypoxia marker carbonic anhydrase IX expressed independently of hypoxia and tumour phenotype

CA IX is a hypoxia-induced, cancer-associated carbonic anhydrase isoform with functional involvement in pH control and cell adhesion. Here we describe an alternative splicing variant of the CA9 mRNA, which does not contain exons 8–9 and is expressed in tumour cells independently of hypoxia. It is also detectable in normal tissues in the absence of the full-length transcript and can therefore produce false-positive data in prognostic studies based on the detection of the hypoxia- and cancer-related CA9 expression. The splicing variant encodes a truncated CA IX protein lacking the C-terminal part of the catalytic domain. It shows diminished catalytic activity and is intracellular or secreted. When overexpressed, it reduces the capacity of the full-length CA IX protein to acidify extracellular pH of hypoxic cells and to bind carbonic anhydrase inhibitor. HeLa cells transfected with the splicing variant cDNA generate spheroids that do not form compact cores, suggesting that they fail to adapt to hypoxic stress. Our data indicate that the splicing variant can functionally interfere with the full-length CA IX. This might be relevant particularly under conditions of mild hypoxia, when the cells do not suffer from severe acidosis and do not need excessive pH control

Ectodomain shedding of the hypoxia-induced carbonic anhydrase IX is a metalloprotease-dependent process regulated by TACE/ADAM17

Carbonic anhydrase IX (CA IX) is a transmembrane protein whose expression is strongly induced by hypoxia in a broad spectrum of human tumours. It is a highly active enzyme functionally involved in both pH control and cell adhesion. Its presence in tumours usually indicates poor prognosis. Ectodomain of CA IX is detectable in the culture medium and body fluids of cancer patients, but the mechanism of its shedding has not been thoroughly investigated. Here, we analysed several cell lines with natural and ectopic expression of CA IX to show that its ectodomain release is sensitive to metalloprotease inhibitor batimastat (BB-94) and that hypoxia maintains the normal rate of basal shedding, thus leading to concomitant increase in cell-associated and extracellular CA IX levels. Using CHO-M2 cells defective in shedding, we demonstrated that the basal CA IX ectodomain release does not require a functional TNFα-converting enzyme (TACE/ADAM17), whereas the activation of CA IX shedding by both phorbol-12-myristate-13-acetate and pervanadate is TACE-dependent. Our results suggest that the cleavage of CA IX ectodomain is a regulated process that responds to physiological factors and signal transduction stimuli and may therefore contribute to adaptive changes in the protein composition of tumour cells and their microenvironment

The calcium-binding protein S100P in normal and malignant human tissues

<p>Abstract</p> <p>Background</p> <p>S100P is a Ca²⁺binding protein overexpressed in a variety of cancers, and thus, has been considered a potential tumor biomarker. Very little has been studied about its normal expression and functions.</p> <p>Methods</p> <p>We examined S100P expression in normal human tissues by quantitative reverse transcription polymerase chain reaction and immunohistochemistry. S100P protein expression was also studied in a series of tumors, consisting of 74 ovarian, 11 pancreatic, 56 gastric, 57 colorectal, 89 breast and 193 prostate carcinomas using a novel anti-S100P monoclonal antibody.</p> <p>Results</p> <p>Among the normal tissues, the highest S100P mRNA levels were observed in the placenta and esophagus. Moderate signals were also detected in the stomach, duodenum, large intestine, prostate and leukocytes. At the protein level, the highest reactions for S100P were seen in the placenta and stomach. Immunostaining of tumor specimens showed that S100P protein is expressed in all the tumor categories included in the study, being most prevalent in gastric tumors.</p> <p>Conclusion</p> <p>Based on our observations, S100P is widely expressed in both normal and malignant tissues. The high expression in some tumors suggests that it may represent a potential target molecule for future diagnostic and therapeutic applications.</p

Hypoxia-regulated carbonic anhydrase IX expression is associated with poor survival in patients with invasive breast cancer.

Tumour hypoxia is a microenvironmental factor related to poor response to radiation, chemotherapy, genetic instability, selection for resistance to apoptosis, and increased risk of invasion and metastasis. Hypoxia-regulated carbonic anhydrase IX (CA IX) has been studied in various tumour sites and its expression has been correlated with the clinical outcome. The purpose of this study was to investigate the correlation of CA IX expression with outcome in patients with invasive breast cancer. We conducted a retrospective study examining the effects of carbonic anhydrase IX (CA IX) on survival in patients with breast cancer. To facilitate the screening of multiple tissue blocks from each patient, tissue microarrays were prepared containing between two and five representative samples of tumour per patient. Immunohistochemistry was used to examine expression of CA IX in patients with breast cancer. The study includes a cohort of 144 unselected patients with early invasive breast cancer who underwent surgery, and had CA IX expression and follow-up data available for analysis. At the time of analysis, there were 28 deaths and median follow-up of 48 months with 96% of patients having at least 2 years of follow-up. CA IX was negative for 107 patients (17 deaths) and positive for 37 patients (11 deaths). Kaplan-Meier survival curves show that survival was superior in the CA IX-negative group with a 2-year survival of 97% for negatives and 83% for positives (log-rank test P=0.01). Allowing for potential prognostic variables in a Cox regression analysis, CA IX remained a significant independent predictor of survival (P=0.035). This study showed in both univariate and multivariate analysis that survival is significantly inferior in patients with tumour expressing CA IX. Prospective studies are underway to investigate this correlation in clinical trial setting

Expression of carbonic anhydrase IX suggests poor outcome in rectal cancer

The aim of the study is to assess the value of carbonic anhydrase isozyme IX (CA IX) expression as a predictor of disease-free survival (DFS) and disease-specific survival (DSS) in rectal cancer treated by preoperative radio- or chemoradiotherapy or surgery only. Archival tumour samples from 166 patients were analysed for CA IX expression by three different evaluations: positive/negative, proportion of positivity and staining intensity. The results of immunohistochemical analysis were confirmed by demonstrating CA IX protein in western blotting analysis. Forty-four percent of the operative samples were CA IX positive, of these 34% had weak and 66% moderate/strong staining intensity. In univariate survival analysis, intensity of CA IX expression was a predictor of DFS (P=0.003) and DSS (P=0.034), both being markedly longer in tumours with negative or weakly positive staining. In multivariate Cox model, number of metastatic lymph nodes and CA IX intensity were the only independent predictors of DFS. Carbonic anhydrase isozyme IX intensity was the only independent predictor of DSS, with HR=9.2 for dying of disease with moderate-intense CA IX expression as compared with CA IX-negative/weak cases. Negative/weak CA IX staining intensity is an independent predictor of longer DFS and DSS in rectal cancer