Background And Purpose: NO produces arteriolar flow-induced dilation (FID) in healthy subjects but is replaced by mitochondria-derived hydrogen peroxide (mtH O ) in patients with coronary artery disease (CAD). Lysophosphatidic acid (LPA) is elevated in patients with risk factors for CAD, but its functional effect in arterioles is unknown. We tested whether elevated LPA changes the mediator of FID from NO to mtH O in human visceral and subcutaneous adipose arterioles.
View Article and Find Full Text PDFIt remains unclear to what extent tumor heterogeneity impacts on protein biomarker discovery. Here, we quantified proteome intra-tissue heterogeneity (ITH) based on a multi-region analysis of prostate tissues using pressure cycling technology and SWATH mass spectrometry. We quantified 6,873 proteins and analyzed the ITH of 3,700 proteins.
View Article and Find Full Text PDFIn order to overcome the limitations of silicon-based electronics, the integration of optically active III-V compounds is a promising approach. Nonetheless, their integration is far from trivial and control as well as understanding of corresponding growth kinetics, and in particular the occurrence and termination of antiphase defects, is of great relevance. In this work, we focus on the three-dimensional reconstruction of such boundaries in gallium phosphide from single scanning transmission electron microscopy images.
View Article and Find Full Text PDFThe neural crest (NC) is a transient embryonic cell population that migrates extensively during development. Ric-8A, a guanine nucleotide exchange factor (GEF) for different Gα subunits regulates cranial NC (CNC) cell migration in Xenopus through a mechanism that still remains to be elucidated. To properly migrate, CNC cells establish an axis of polarization and undergo morphological changes to generate protrusions at the leading edge and retraction of the cell rear.
View Article and Find Full Text PDFWe report the formation of Bi clusters in Ga(P,Bi) layers during an in situ (scanning) transmission electron microscopy ((S)TEM) annealing investigation. The non-destructive temperature regime in dependence on the tertiarybutylphosphine (TBP) pressure in the in situ cell was investigated to ensure that the results are not distorted by any destructive behaviour of the crystal during the thermal treatment. The following annealing series of the Ga(PBi) and Ga(PBi) layers reveals that the threshold temperature at which the Bi clustering takes place is 600 °C in the Ga(PBi) layer.
View Article and Find Full Text PDFThe provision of clean water is a global challenge, and membrane filtration is a key technology to address it. Conventional filtration membranes are constrained by a trade-off between permeance and selectivity. Recently, some nanostructured membranes demonstrated the ability to overcome this limitation by utilizing well-defined carbon nanoconduits that allow a coordinated passage of water molecules.
View Article and Find Full Text PDFAlthough chemotherapeutics can be highly effective at targeting malignancies, their ability to trigger cardiovascular morbidity is clinically significant. Chemotherapy can adversely affect cardiovascular physiology, resulting in the development of cardiomyopathy, heart failure and microvascular defects. Specifically, anthracyclines are known to cause an excessive buildup of free radical species and mitochondrial DNA damage (DNA) that can lead to oxidative stress-induced cardiovascular apoptosis.
View Article and Find Full Text PDFIn diseases of many parenchymatous organs, heterogeneous deterioration of individual functional units determines the clinical prognosis. However, the molecular characterization at the level of such individual subunits remains a technological challenge that needs to be addressed in order to better understand pathological mechanisms. Proteinuric glomerular kidney diseases are frequent and assorted diseases affecting a fraction of glomeruli and their draining tubules to variable extents, and for which no specific treatment exists.
View Article and Find Full Text PDFObjective: We explored mechanisms that alter mitochondrial structure and function in pulmonary endothelial cells (PEC) function after hyperoxia.
Approach And Results: Mitochondrial structures of PECs exposed to hyperoxia or normoxia were visualized and mitochondrial fragmentation quantified. Expression of pro-fission or fusion proteins or autophagy-related proteins were assessed by Western blot.
Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz
April 2018
Background: There is a connection between the receipt of unemployment benefits and the failure to use contraceptives in Germany. This study aims to understand the use of contraceptives among women entitled to unemployment benefits under the Sozialgesetzbuch II or XII (SGB II or SGB XII), prior and during an offer of contraceptives free of charge (CFOC).
Methods: The criteria for the use of CFOC (pill, intrauterine device, or ring) over a 12-month period were: age between 20 and 35 years, resident in predefined urban or rural postal codes in the German federal state of Mecklenburg-Western Pomerania, and participation in a self-administered survey.
Derivation of human hematopoietic stem cells (HSCs) from induced pluripotent stem cells (iPSCs) offers considerable promise for cell therapy, disease modeling, and drug screening. However, efficient derivation of functional iPSC-derived HSCs with in vivo engraftability and multilineage potential remains challenging. Here, we demonstrate a tractable approach for respecifying iPSC-derived blood cells into highly engraftable hematopoietic stem and progenitor cells (HSPCs) through transient expression of a single transcription factor, These induced HSPCs (iHSPCs) derived from iPSCs are able to fully reconstitute the human hematopoietic system in the recipient mice without myeloid bias.
View Article and Find Full Text PDFSurface-enhanced Raman scattering spectroscopy (SERS) was employed to investigate the formation of self-assembled monolayers (SAMs) of biphenylthiol, 4'-nitro-1,1'-biphenyl-4-thiol, and p-terphenylthiol on Au surfaces and their structural transformations into carbon nanomembranes (CNMs) induced by electron irradiation. The high sensitivity of SERS allows us to identify two types of Raman scattering in electron-irradiated SAMs: (1) Raman-active sites exhibit similar bands as those of pristine SAMs in the fingerprint spectral region, but with indications of an amorphization process and (2) Raman-inactive sites show almost no Raman-scattering signals, except a very weak and broad D band, indicating a lack of structural order but for the presence of graphitic domains. Statistical analysis showed that the ratio of the number of Raman-active sites to the total number of measurement sites decreases exponentially with increasing the electron irradiation dose.
View Article and Find Full Text PDFBackground: In naive rats, corticosteroids activate neuronal membrane-bound glucocorticoid and mineralocorticoid receptors in spinal cord and periphery to modulate nociceptive behavior by nongenomic mechanisms. Here we investigated inflammation-induced changes in neuronal versus glial glucocorticoid and mineralocorticoid receptors and their ligand-mediated nongenomic impact on mechanical nociception in rats.
Methods: In Wistar rats (n = 5 to 7/group) with Freund's complete adjuvant hind paw inflammation, we examined glucocorticoid and mineralocorticoid receptor expression in spinal cord and peripheral sensory neurons versus glial using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blot, immunohistochemistry, and radioligand binding.
A rise in reactive oxygen species (ROS) may contribute to cardiovascular disease by reducing nitric oxide (NO) levels, leading to loss of NO's vasodilator and anti-inflammatory effects. Although primarily studied in larger conduit arteries, excess ROS release and a corresponding loss of NO also occur in smaller resistance arteries of the microcirculation, but the underlying mechanisms and therapeutic targets have not been fully characterized. We examined whether either of the two subunits of telomerase, telomerase reverse transcriptase (TERT) or telomerase RNA component (TERC), affect microvascular ROS production and peak vasodilation at baseline and in response to in vivo administration to angiotensin II (ANG II).
View Article and Find Full Text PDFNuclear transport receptors (NTRs) recognize localization signals of cargos to facilitate their passage across the central channel of nuclear pore complexes (NPCs). About 30 different NTRs constitute different transport pathways in humans and bind to a multitude of different cargos. The exact cargo spectrum of the majority of NTRs, their specificity and even the extent to which active nucleocytoplasmic transport contributes to protein localization remains understudied because of the transient nature of these interactions and the wide dynamic range of cargo concentrations.
View Article and Find Full Text PDFDuring prenatal development the liver is composed of multiple cell types with unique properties compared to their adult counterparts. We aimed to establish multilineage cultures of human fetal liver cells that could maintain stem cell and progenitor populations found in the developing liver. An aim of this study was to test if maturation of fetal hepatocytes in short-term cultures supported by epidermal growth factor and oncostatin M can improve their ability to engraft immunodeficient mice.
View Article and Find Full Text PDFKnowledge of the microscopic elemental composition of multinary III/V semiconductor materials is crucial to the development of functionalized opto-electronic devices. Well-proven composition analysis methods, such as high resolution X-ray diffraction (HRXRD), fail to determine the elemental composition when more than three atomic species are involved. In this work we propose a procedure for the composition analysis of multinary III/V semiconductors at atomic resolution using high angle annular dark field (HAADF) scanning transmission electron microscopy (STEM) image simulations.
View Article and Find Full Text PDFAnthrax, caused by Bacillus anthracis, is considered a severe bioterrorism threat because of its high mortality rate. The Chicago Healthcare System Coalition for Preparedness and Response (CHSCPR) aims to pre-position antibiotic medical countermeasures (MCMs) at healthcare facilities in order to provide on-site anthrax post-exposure prophylaxis. Pharmacists proposed moving toward a new process that involved the development of a standardized calculation methodology for acquiring supply drugs.
View Article and Find Full Text PDFFor photon-counting applications at ultraviolet wavelengths, there are currently no detectors that combine high efficiency (> 50%), sub-nanosecond timing resolution, and sub-Hz dark count rates. Superconducting nanowire single-photon detectors (SNSPDs) have seen success over the past decade for photon-counting applications in the near-infrared, but little work has been done to optimize SNSPDs for wavelengths below 400 nm. Here, we describe the design, fabrication, and characterization of UV SNSPDs operating at wavelengths between 250 and 370 nm.
View Article and Find Full Text PDFDown syndrome (DS) is mostly caused by a trisomy of the entire Chromosome 21 (Trisomy 21, T21). Here, we use SWATH mass spectrometry to quantify protein abundance and protein turnover in fibroblasts from a monozygotic twin pair discordant for T21, and to profile protein expression in 11 unrelated DS individuals and matched controls. The integration of the steady-state and turnover proteomic data indicates that protein-specific degradation of members of stoichiometric complexes is a major determinant of T21 gene dosage outcome, both within and between individuals.
View Article and Find Full Text PDFAt the core of the "proton radius puzzle" is a four-standard deviation discrepancy between the proton root-mean-square charge radii () determined from the regular hydrogen (H) and the muonic hydrogen (µp) atoms. Using a cryogenic beam of H atoms, we measured the 2S-4P transition frequency in H, yielding the values of the Rydberg constant = 10973731.568076(96) per meterand = 0.
View Article and Find Full Text PDFBioinformatics
January 2018
Summary: Gene expression alterations and potentially underlying gene copy number mutations can be measured routinely in the wet lab, but it is still extremely challenging to quantify impacts of altered genes on clinically relevant characteristics to predict putative driver genes. We developed the R package regNet that utilizes gene expression and copy number data to learn regulatory networks for the quantification of potential impacts of individual gene expression alterations on user-defined target genes via network propagation. We demonstrate the value of regNet by identifying putative major regulators that distinguish pilocytic from diffuse astrocytomas and by predicting putative impacts of glioblastoma-specific gene copy number alterations on cell cycle pathway genes and patient survival.
View Article and Find Full Text PDFThe atomic structure of (GaIn)As/Ga(AsSb)/(GaIn)As-'W'-type quantum well heterostructures ('W'-QWHs) is investigated by scanning transmission electron microscopy (STEM). These structures were grown by metal organic vapour phase epitaxy and are built for type-II laser systems in the infrared wavelength regime. For two samples grown at 525°C and 550°C, intensity profiles are extracted from the STEM images for each sublattice separately.
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