132 research outputs found
Triplet Supercurrents in clean and disordered half-metallic ferromagnets
Interfaces between materials with differently ordered phases present unique opportunities to study fundamental problems in physics. One example is the interface between a singlet superconductor and a half-metallic ferromagnet, where Cooper pairing occurs between electrons with opposite spin on the superconducting side, whereas the other exhibits 100% spin polarization. The recent surprising observation of a supercurrent through half-metallic CrO2 therefore requires a mechanism for conversion between unpolarized and completely spin-polarized supercurrents. Here, we suggest a conversion mechanism based on electron spin precession together with triplet-pair rotation at interfaces with broken spin-rotation symmetry. In the diffusive limit (short mean free path), the triplet supercurrent is dominated by inter-related odd-frequency s-wave and even-frequency p-wave pairs. In the crossover to the ballistic limit, further symmetry components become relevant. The interface region exhibits a superconducting state of mixed-spin pairs with highly unusual symmetry properties that open up new perspectives for exotic Josephson devices
Disulphide bond reduction of a therapeutic monoclonal antibody during cell culture manufacturing operations
3-Methyl-1-butanol production in Escherichia coli: random mutagenesis and two-phase fermentation
Interest in producing biofuels from renewable sources has escalated due to energy and environmental concerns. Recently, the production of higher chain alcohols from 2-keto acid pathways has shown significant progress. In this paper, we demonstrate a mutagenesis approach in developing a strain of Escherichia coli for the production of 3-methyl-1-butanol by leveraging selective pressure toward l-leucine biosynthesis and screening for increased alcohol production. Random mutagenesis and selection with 4-aza-d,l-leucine, a structural analogue to l-leucine, resulted in the development of a new strain of E. coli able to produce 4.4 g/L of 3-methyl-1-butanol. Investigation of the host’s sensitivity to 3-methyl-1-butanol directed development of a two-phase fermentation process in which titers reached 9.5 g/L of 3-methyl-1-butanol with a yield of 0.11 g/g glucose after 60 h
Roles of AP-2 in clathrin-mediated endocytosis.
The notion that AP-2 clathrin adaptor is an essential component of an endocytic clathrin coat appears to conflict with recent observations that substantial AP-2 depletion, using RNA interference with synthesis of AP-2 subunits, fails to block uptake of certain ligands known to internalize through a clathrin-based pathway
Chronic Obstructive Pulmonary Disease Is Associated with Low Levels of Vitamin D
Introduction: COPD patients may be at increased risk for vitamin D (25(OH)D) deficiency, but risk factors for deficiency among COPD patients have not been extensively reported. Methods: Serum 25(OH)D levels were measured by liquid chromatography double mass spectrometry in subjects aged 40–76 years from Western Norway, including 433 COPD patients (GOLD stage II-IV) and 325 controls. Levels <20 ng/mL defined deficiency. Season, sex, age, body mass index (BMI), smoking, GOLD stage, exacerbation frequency, arterial oxygen tension (PaO2), respiratory symptoms, depression (CES-D score≥16), comorbidities (Charlson score), treatment for osteoporosis, use of inhaled steroids, and total white blood count were examined for associations with 25(OH)D in both linear and logistic regression models. Results: COPD patients had an increased risk for vitamin D deficiency compared to controls after adjustment for seasonality, age, smoking and BMI. Variables associated with lower 25(OH)D levels in COPD patients were obesity ( = −6.63), current smoking ( = −4.02), GOLD stage III- IV ( = −4.71, = −5.64), and depression ( = −3.29). Summertime decreased the risk of vitamin D deficiency (OR = 0.22). Conclusion: COPD was associated with an increased risk of vitamin D deficiency, and important disease characteristics were significantly related to 25(OH)D levels
Contrast in Edge Vegetation Structure Modifies the Predation Risk of Natural Ground Nests in an Agricultural Landscape
Nest predation risk generally increases nearer forest-field edges in agricultural landscapes. However, few studies test whether differences in edge contrast (i.e. hard versus soft edges based on vegetation structure and height) affect edge-related predation patterns and if such patterns are related to changes in nest conspicuousness between incubation and nestling feeding. Using data on 923 nesting attempts we analyse factors influencing nest predation risk at different edge types in an agricultural landscape of a ground-cavity breeding bird species, the Northern Wheatear (Oenanthe oenanthe). As for many other bird species, nest predation is a major determinant of reproductive success in this migratory passerine. Nest predation risk was higher closer to woodland and crop field edges, but only when these were hard edges in terms of ground vegetation structure (clear contrast between tall vs short ground vegetation). No such edge effect was observed at soft edges where adjacent habitats had tall ground vegetation (crop, ungrazed grassland). This edge effect on nest predation risk was evident during the incubation stage but not the nestling feeding stage. Since wheatear nests are depredated by ground-living animals our results demonstrate: (i) that edge effects depend on edge contrast, (ii) that edge-related nest predation patterns vary across the breeding period probably resulting from changes in parental activity at the nest between the incubation and nestling feeding stage. Edge effects should be put in the context of the nest predator community as illustrated by the elevated nest predation risk at hard but not soft habitat edges when an edge is defined in terms of ground vegetation. These results thus can potentially explain previously observed variations in edge-related nest predation risk
Inclusion of maintenance energy improves the intracellular flux predictions of CHO
Chinese hamster ovary (CHO) cells are the leading platform for the production of biopharmaceuticals with human-like glycosylation. The standard practice for cell line generation relies on trial and error approaches such as adaptive evolution and high-throughput screening, which typically take several months. Metabolic modeling could aid in designing better producer cell lines and thus shorten development times. The genome-scale metabolic model (GSMM) of CHO can accurately predict growth rates. However, in order to predict rational engineering strategies it also needs to accurately predict intracellular fluxes. In this work we evaluated the agreement between the fluxes predicted by parsimonious flux balance analysis (pFBA) using the CHO GSMM and a wide range of 13C metabolic flux data from literature. While glycolytic fluxes were predicted relatively well, the fluxes of tricarboxylic acid (TCA) cycle were vastly underestimated due to too low energy demand. Inclusion of computationally estimated maintenance energy significantly improved the overall accuracy of intracellular flux predictions. Maintenance energy was therefore determined experimentally by running continuous cultures at different growth rates and evaluating their respective energy consumption. The experimentally and computationally determined maintenance energy were in good agreement. Additionally, we compared alternative objective functions (minimization of uptake rates of seven nonessential metabolites) to the biomass objective. While the predictions of the uptake rates were quite inaccurate for most objectives, the predictions of the intracellular fluxes were comparable to the biomass objective function.COMET center acib: Next Generation
Bioproduction, which is funded by BMK, BMDW,
SFG, Standortagentur Tirol, Government of Lower
Austria and Vienna Business Agency in the
framework of COMET - Competence Centers for
Excellent Technologies. The COMET-Funding
Program is managed by the Austrian Research
Promotion Agency FFG; D.S., J.S., M.W., M.H., D.
E.R. This work has also been supported by the PhD
program BioToP of the Austrian Science Fund
(FWF Project W1224)info:eu-repo/semantics/publishedVersio
Computational Identification of Uncharacterized Cruzain Binding Sites
Chagas disease, caused by the unicellular parasite Trypanosoma cruzi, claims 50,000 lives annually and is the leading cause of infectious myocarditis in the world. As current antichagastic therapies like nifurtimox and benznidazole are highly toxic, ineffective at parasite eradication, and subject to increasing resistance, novel therapeutics are urgently needed. Cruzain, the major cysteine protease of Trypanosoma cruzi, is one attractive drug target. In the current work, molecular dynamics simulations and a sequence alignment of a non-redundant, unbiased set of peptidase C1 family members are used to identify uncharacterized cruzain binding sites. The two sites identified may serve as targets for future pharmacological intervention
<em>Enterococcus faecalis</em> Infection Causes Inflammation, Intracellular Oxphos-Independent ROS Production, and DNA Damage in Human Gastric Cancer Cells
Background: Achlorhydria caused by e.g. atrophic gastritis allows for bacterial overgrowth, which induces chronic inflammation and damage to the mucosal cells of infected individuals driving gastric malignancies and cancer. Enterococcus faecalis (E. faecalis) can colonize achlohydric stomachs and we therefore wanted to study the impact of E. faecalis infection on inflammatory response, reactive oxygen species (ROS) formation, mitochondrial respiration, and mitochondrial genetic stability in gastric mucosal cells. Methods: To separate the changes induced by bacteria from those of the inflammatory cells we established an in vitro E. faecalis infection model system using the gastric carcinoma cell line MKN74. Total ROS and superoxide was measured by fluorescence microscopy. Cellular oxygen consumption was characterized non-invasively using XF24 microplate based respirometry. Gene expression was examined by microarray, and response pathways were identified by Gene Set Analysis (GSA). Selected gene transcripts were verified by quantitative real-time polymerase chain reaction (qRT-PCR). Mitochondrial mutations were determined by sequencing. Results: Infection of MKN74 cells with E. faecalis induced intracellular ROS production through a pathway independent of oxidative phosphorylation (oxphos). Furthermore, E. faecalis infection induced mitochondrial DNA instability. Following infection, genes coding for inflammatory response proteins were transcriptionally up-regulated while DNA damage repair and cell cycle control genes were down-regulated. Cell growth slowed down when infected with viable E. faecalis and responded in a dose dependent manner to E. faecalis lysate. Conclusions: Infection by E. faecalis induced an oxphos-independent intracellular ROS response and damaged the mitochondrial genome in gastric cell culture. Finally the bacteria induced an NF-kappa B inflammatory response as well as impaired DNA damage response and cell cycle control gene expression
Genetic and phenotypic spectrum associated with IFIH1 gain-of-function
IFIH1 gain-of-function has been reported as a cause of a type I interferonopathy encompassing a spectrum of autoinflammatory phenotypes including Aicardi–Goutières syndrome and Singleton Merten syndrome. Ascertaining patients through a European and North American collaboration, we set out to describe the molecular, clinical and interferon status of a cohort of individuals with pathogenic heterozygous mutations in IFIH1. We identified 74 individuals from 51 families segregating a total of 27 likely pathogenic mutations in IFIH1. Ten adult individuals, 13.5% of all mutation carriers, were clinically asymptomatic (with seven of these aged over 50 years). All mutations were associated with enhanced type I interferon signaling, including six variants (22%) which were predicted as benign according to multiple in silico pathogenicity programs. The identified mutations cluster close to the ATP binding region of the protein. These data confirm variable expression and nonpenetrance as important characteristics of the IFIH1 genotype, a consistent association with enhanced type I interferon signaling, and a common mutational mechanism involving increased RNA binding affinity or decreased efficiency of ATP hydrolysis and filament disassembly rate
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