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Hypoxia regulates global membrane protein endocytosis through caveolin-1 in cancer cells

Hypoxia promotes tumour aggressiveness and resistance of cancers to oncological treatment. The identification of cancer cell internalizing antigens for drug targeting to the hypoxic tumour niche remains a challenge of high clinical relevance. Here we show that hypoxia down-regulates the surface proteome at the global level and, more specifically, membrane proteome internalization. We find that hyp

Fetal hemoglobin, α1-microglobulin and hemopexin are potential predictive first trimester biomarkers for preeclampsia

Objective Overproduction of cell-free fetal hemoglobin (HbF) in the preeclamptic placenta has been recently implicated as a new etiological factor of preeclampsia. In this study, maternal serum levels of HbF and the endogenous hemoglobin/heme scavenging systems were evaluated as predictive biomarkers for preeclampsia in combination with uterine artery Doppler ultrasound. Study design Case-control

Pseudomonas aeruginosa elastase cleaves a C-terminal peptide from human thrombin that inhibits host inflammatory responses

Pseudomonas aeruginosa is an opportunistic pathogen known for its immune evasive abilities amongst others by degradation of a large variety of host proteins. Here we show that digestion of thrombin by P. aeruginosa elastase leads to the release of the C-terminal thrombin-derived peptide FYT21, which inhibits pro-inflammatory responses to several pathogen-associated molecular patterns in vitro and

Aromatase inhibitors alone or sequentially combined with tamoxifen in postmenopausal early breast cancer compared with tamoxifen or placebo - Meta-analyses on efficacy and adverse events based on randomized clinical trials

Tamoxifen (TAM) and aromatase inhibitors (AI) are adjuvant therapy options for postmenopausal women with estrogen receptor positive (ER+) breast cancer. This systematic review of seven randomized controlled studies comparing TAM and AI, and one study comparing extended therapy with an AI with placebo after about 5 years of tamoxifen, aims to assess long-term clinical efficacy and adverse events. T

Interactive effects of physical fitness and body mass index on risk of stroke : A national cohort study

BACKGROUND: High body mass index (BMI) and low physical fitness are risk factors for stroke, but their interactive effects are unknown. Elucidation of interactions between these modifiable risk factors can help inform preventive interventions in susceptible subgroups.METHODS: National cohort study of all 1,547,294 military conscripts in Sweden during 1969-1997 (97-98% of all 18-year-old males). St

Neuropeptide Y (NPY) in cerebrospinal fluid from patients with Huntington's Disease : increased NPY levels and differential degradation of the NPY1-30 fragment

Huntington's disease (HD) is an inherited and fatal polyglutamine neurodegenerative disorder caused by an expansion of the CAG triplet repeat coding region within the HD gene. Progressive dysfunction and loss of striatal GABAergic medium spiny neurons (MSNs) may account for some of the characteristic symptoms in HD patients. Interestingly, in HD, MSNs expressing neuropeptide Y (NPY) are spared and

Fracture epidemiology in male elite football players from 2001 to 2013: 'How long will this fracture keep me out?'

BACKGROUND: Determining fracture risk and rehabilitation periods after specific fractures in professional football is essential for team planning.AIM: To identify fracture epidemiology and absences after different types of fractures in male professional football players.METHODS: 2439 players from 41 professional male teams in 10 countries were followed prospectively from 2001 to 2013. Team medical

Marine silicon cycle through the Cenozoic

Omsättningen av kisel (Si) är en av de viktiga biogeokemiska processerna på jorden. Den lösta formen av Si (DSi) är ett nödvändigt näringsämne för såväl markens som havens ekosystem. Löst kisel kommer från den långsamma kemiska vittringen av kiselmineral. Denna process förbrukar koldioxid och bidrar därför till att reglera jordens klimat genom årmiljonerna. Kisel transporteras huvudsakligen via odSilicon (Si) cycle is one of Earth's major biogeochemical cycles. Furthermore, the dissolved form of Si (DSi) is an essential nutrient for both terrestrial and marine ecosystems. DSi ultimately derives from the slow process of chemical weathering of silicate minerals, a mechanism that consumes carbon dioxide, and therefore participates in regulating Earth's climate over geologic timescales. Si is

Identification of Non-HLA Genes Associated with Celiac Disease and Country-Specific Differences in a Large, International Pediatric Cohort

OBJECTIVES: There are significant geographical differences in the prevalence and incidence of celiac disease that cannot be explained by HLA alone. More than 40 loci outside of the HLA region have been associated with celiac disease. We investigated the roles of these non-HLA genes in the development of tissue transglutaminase autoantibodies (tTGA) and celiac disease in a large international prosp

Frequent mismatch-repair defects link prostate cancer to Lynch syndrome

BACKGROUND: A possible role for prostate cancer in Lynch syndrome has been debated based on observations of mismatch-repair defective tumors and reports of an increased risk of prostate cancer in mutation carriers. Potential inclusion of prostate cancer in the Lynch syndrome tumor spectrum is relevant for family classification, risk estimates and surveillance recommendations in mutation carriers.M

Tyrosine residues as redox cofactors in human hemoglobin : implications for engineering nontoxic blood substitutes

Respiratory proteins such as myoglobin and hemoglobin can, under oxidative conditions, form ferryl heme iron and protein-based free radicals. Ferryl myoglobin can safely be returned to the ferric oxidation state by electron donation from exogenous reductants via a mechanism that involves two distinct pathways. In addition to direct transfer between the electron donor and ferryl heme edge, there is

NAD(H) recycling activity of an engineered bifunctional enzyme galactose dehydrogenase/lactate dehydrogenase

A chimeric bifunctional enzyme composing of galactose dehydrogenase (galDH; from Pseudomonas fluorescens) and lactate dehydrogenase (LDH; from Bacillus stearothermophilus) was successfully constructed. The chimeric galDH/LDH possessed dual characteristics of both galactose dehydrogenase and lactate dehydrogenase activities while exhibiting hexameric rearrangement with a molecular weight of approxi

Improved partitioning in aqueous two-phase system of tyrosine-tagged recombinant lactate dehydrogenase

The partitioning of Bacillus stearothermophilus lactate dehydrogenase (LDH) in an aqueous two-phase system was studied. Particularly, the influence of tyrosine tags on the partitioning was evaluated. The hydrophobic effect, caused by the addition of tyrosine residues, was determined in a system based on dextran and the thermoseparating ethylene oxide-propylene oxide random copolymer (EO30PO70). Fi

Purification and characterization of a beta-lactamase from Haemophilus ducreyi in Escherichia coli

A pCb plasmid encoding a beta-lactamase from Haemophilus ducreyi was transferred to Escherichia coli, purified, and characterized. The beta-lactamase could be isolated from a culture filtrate and further purified by ammonium sulfate and chelating Sepharose fast flow loaded with Zn(2+). The purified enzyme resulted in a major band at approximately 30-kDa on SDS-PAGE and its pI was determined to be

Calorimetric analysis of cephalosporins using an immobilized TEM-1 beta-lactamase on Ni2+ chelating sepharose fast flow

Two beta-lactamases, penicillinase type I from Bacillus cereus and TEM-1 beta-lactamase from Haemophilus ducreyi, were immobilized on a Chelating Sepharose Fast Flow column loaded with Ni2+ in an active form. Flow-injection analysis of beta-lactams was performed by using an enzyme column reactor fitted into the enzyme thermistor. With both enzymes it was possible to monitor both penicillins and ce

Metal-binding proteins and peptides in bioremediation and phytoremediation of heavy metals

The expression of metal-binding proteins or peptides in microorganisms and plants in order to enhance heavy metal accumulation and/or tolerance has great potential. Several different peptides and proteins have been explored. This review focuses on cadmium (Cd) because of the significant importance of this metal and because of its global presence in many food materials.

Error-prone PCR of Vitreoscilla hemoglobin (VHb) to support the growth of microaerobic Escherichia coli

Expression of the gene encoding bacterial hemoglobin (VHb) from Vitreoscilla has been previously used to improve recombinant cell growth and enhance product formation under microaerobic conditions. It is very likely that the properties of VHb are not optimized for foreign hosts; therefore, we used error-prone PCR to generate a number of randomly mutated vhb genes to be expressed and studied in Esc

Redesign of the coenzyme specificity in L-lactate dehydrogenase from bacillus stearothermophilus using site-directed mutagenesis and media engineering

L-lactate dehydrogenase (LDH) from Bacillus stearothermophilus is a redox enzyme which has a strong preference for NADH over NADPH as coenzyme. To exclude NADPH from the coenzyme-binding pocket, LDH contains a conserved aspartate residue at position 52. However, this residue is probably not solely responsible for the NADH specificity. In this report we examine the possibilities of altering the coe