A HIF independent oxygen-sensitive pathway for controlling cholesterol synthesis.

Cholesterol biosynthesis is a highly regulated, oxygen-dependent pathway, vital for cell membrane integrity and growth. In fungi, the dependency on oxygen for sterol production has resulted in a shared transcriptional response, resembling prolyl hydroxylation of Hypoxia Inducible Factors (HIFs) in metazoans. Whether an analogous metazoan pathway exists is unknown.

Role of Hypoxia in the Interferon Response.

In solid tumors, as the tumor grows and the disease progresses, hypoxic regions are often generated, but in contrast to most normal cells which cannot survive under these conditions, tumour cells adapt to hypoxia by HIF-driven mechanisms. Hypoxia can further promote cancer development by generating an immunosuppressive environment within the tumour mass, which allows tumour cells to escape the immune system recognition. This is achieved by recruiting immunosuppressive cells and by upregulating molecules which block immune cell activation.

Hypoxia Regulates Endogenous Double-Stranded RNA Production Reduced Mitochondrial DNA Transcription.

Hypoxia is a common phenomenon in solid tumours strongly linked to the hallmarks of cancer. Hypoxia promotes local immunosuppression and downregulates type I interferon (IFN) expression and signalling, which contribute to the success of many cancer therapies. Double-stranded RNA (dsRNA), transiently generated during mitochondrial transcription, endogenously activates the type I IFN pathway.

Differential effects of HIF2α antagonist and HIF2α silencing in renal cancer and sensitivity to repurposed drugs.

Background: In clear cell renal cell carcinoma, 80% of cases have biallelic inactivation of the VHL gene, leading to constitutive activation of both HIF1α and HIF2α. As HIF2α is the driver of the disease promoting tumour growth and metastasis, drugs targeting HIF2α have been developed. However, resistance is common, therefore new therapies are needed.

Evaluation of Lipoprotein Profile and Residual Risk Three Years After Bariatric Surgery.

Introduction: Obesity is a chronic disease associated with other comorbidities, including atherogenic dyslipidemia (AD). Bariatric surgery (BS) has shown to reduce cardiovascular risk (CVR) by achieving a significant weight reduction and improving the lipid profile. Different surgical techniques may have a different effect on the lipoprotein profile.

The HIF complex recruits the histone methyltransferase SET1B to activate specific hypoxia-inducible genes.

Hypoxia-inducible transcription factors (HIFs) are fundamental to cellular adaptation to low oxygen levels, but it is unclear how they interact with chromatin and activate their target genes. Here, we use genome-wide mutagenesis to identify genes involved in HIF transcriptional activity, and define a requirement for the histone H3 lysine 4 (H3K4) methyltransferase SET1B. SET1B loss leads to a selective reduction in transcriptional activation of HIF target genes, resulting in impaired cell growth, angiogenesis and tumor establishment in SET1B-deficient xenografts.

Biogas-based production of glycogen by Nostoc muscorum: Assessing the potential of transforming CO into value added products.

The potential of the filamentous N-fixing cyanobacterium Nostoc muscorum for CO capture from high-loaded streams (i.e. flue gas or biogas) combined with the accumulation of glycogen (GL) and polyhydroxybutyrate (PHB), was evaluated under nutrient-sufficient and nutrient-limited conditions.

Hypoxia Induces Transcriptional and Translational Downregulation of the Type I IFN Pathway in Multiple Cancer Cell Types.

Hypoxia is a common phenomenon in solid tumors and is strongly linked to hallmarks of cancer. Recent evidence has shown that hypoxia promotes local immune suppression. Type I IFN supports cytotoxic T lymphocytes by stimulating the maturation of dendritic cells and enhancing their capacity to process and present antigens.

Trimethylamine abatement in algal-bacterial photobioreactors.

Trimethylamine (TMA) is an odorous volatile organic compound emitted by industries. Algal-based biotechnologies have been proven as a feasible alternative for wastewater treatment, although their application to abate polluted air emissions is still scarce. This work comparatively assessed the removal of TMA in a conventional bacterial bubble column bioreactor (BC) and a novel algal-bacterial bubble column photobioreactor (PBC).

Elucidating the influence of environmental factors on biogas-based polyhydroxybutyrate production by Methylocystis hirsuta CSC1.

The valorization of biogas as a feedstock for the generation of added-value bioproducts will play a key role on the sustainability of anaerobic digestion. The present work assessed the influence of key environmental parameters (O:CH ratio, temperature and nitrogen source) on the growth and polyhydroxybutyrate (PHB) synthesis under nitrogen limiting conditions of the type II methanotroph Methylocystis hirsuta CSC1 using biogas as a feedstock. The O:CH ratios tested (1:1, 1.

The circulating transcriptome as a source of cancer liquid biopsy biomarkers.

Non-invasive biomarkers or liquid biopsies have the potential to revolutionise cancer patient management as repeated sampling allows real-time monitoring of disease progression and response to treatment. This allows for earlier intervention and dynamic treatment management; both cornerstones of personalised medicine. The circulating transcriptome represents a rich source of potential cancer biomarkers that includes many classes of RNA, both coding and non-coding, that are only now beginning to be explored.

CircRNAs and cancer: Biomarkers and master regulators.

Circular RNAs (circRNAs) are a novel class of regulatory RNAs that despite being relatively abundant have only recently begun to be explored. There are many thousands of genes that appear capable of producing circRNAs, however the function of all but a handful remain to be determined. What is emerging about these highly conserved molecules is that they play important roles in biology and cancer biology in particular.

MicroRNAs as Biomarkers of B-cell Lymphoma.

B-cell lymphomas represent a diverse group of neoplasms classified primarily by histopatholgy and are often challenging to accurately diagnose. Despite having been recognized less than 20 years ago, microRNAs (miRNAs) have emerged as one of the most promising class of cancer molecular biomarkers and are particularly attractive as they can be readily detected in formalin-fixed paraffin-embedded biopsy material and biological fluids such as blood. Many of the identified B-cell lymphoma miRNA biomarkers also play crucial regulatory roles in normal B-cell development.

Nitrous Oxide Abatement Coupled with Biopolymer Production As a Model GHG Biorefinery for Cost-Effective Climate Change Mitigation.

NO represents ∼6% of the global greenhouse gas emission inventory and the most important O-depleting substance emitted in this 21st century. Despite its environmental relevance, little attention has been given to cost-effective and environmentally friendly NO abatement methods. Here we examined, the potential of a bubble column (BCR) and an internal loop airlift (ALR) bioreactors of 2.

Synergistic activity of carbosilane dendrimers in combination with maraviroc against HIV in vitro.

Objective: Dendrimers have been shown as effective and safe anti-HIV compounds with great potential as topical microbicides. Currently, the most advanced microbicides are based on antiretrovirals. However, nowadays none of them has shown any success in clinical trials.

Supercritical fluid extraction of free amino acids from broccoli leaves.

The extraction of free amino acids (AAs) from broccoli leaves using supercritical fluid extraction (SFE) with CO(2) modified with methanol, is presented in this work. The effect of the different variables was studied, showing the percentage of methanol a strong influence on the extraction. The best results in terms of extraction yield were obtained at 250 bar, 70°C, 35% methanol as organic modifier, a flow rate of 2 mL/min, and 5 min and 30 min as static and dynamic extraction times, respectively.

Synthesis of cationic carbosilane dendrimers via click chemistry and their use as effective carriers for DNA transfection into cancerous cells.

New amine-terminated carbosilane dendrimers have been prepared by a Huisgen cycloaddition ("click chemistry" reaction) of azide-terminated carbosilane dendrimers with two different propargyl amines. The corresponding cationic derivatives with peripheral ammonium groups were obtained by subsequent addition of MeI. Quaternized dendrimers are soluble and stable in water or other protic solvents for long time periods, and have been studied as nonviral vectors for the transfection of DNA to cancer cells.

Comprehensive two-dimensional gas chromatography with capillary flow modulation to separate FAME isomers.

A method to separate FAME and the linoleic and linolenic acids isomers by GCxGC using an apparatus equipped with a capillary flow technology (CFT) based modulator and a FID detector has been developed. Four different column combinations (one conventional and three inverted phase sets) were used in these experiments. The conventional set first involved a DB5-MS non-polar column followed by a highly polar HP-INNOWax column in the second dimension.

Surgical treatment of arterial ischemia associated with the use of the angioseal vascular closure device.

Background: Despite the theoretical effectiveness of the Angio-Seal closure device to control bleeding after arterial puncture it can increase the risk of ischemia.

Objectives: To describe arterial lesions caused by the device, surgical techniques needed to repair those lesions and surgical outcome in patients who underwent surgery for arterial ischemia after heart catheterization.

Patients And Methods: Seven patients underwent surgery over a period of 12 months at our institution.

Repeat mitral valve replacement: 30-years' experience.

Prosthetic heart valve dysfunction is an acquired condition that carries a significant risk of emergency surgery. However, the long-term natural history of the condition is not well understood. Between 1974 and 2006, 1535 isolated mitral valve replacements were performed at our hospital (in-hospital mortality 5%).