Search

Blood–brain barrier (BBB) disruption, resulting from loss of tight junctions (TJ) and activation of matrix metalloproteinases (MMPs), is associated with edema formation in ischemic stroke. Cerebral edema develops in a phasic manner and consists of both vasogenic and cytotoxic components. Although it is contingent on several independent mechanisms, involving hypoxic and inflammatory responses, the single effect of prolonged hypoxia on BBB integrity in vivo was not addressed so far. Exposing mice to normobaric hypoxia (8% oxygen for 48 h) led to a significant increase in vascular permeability associated with diminished expression of the TJ protein occludin. Immunofluorescence studies revealed that hypoxia resulted in disrupted continuity of occludin and zonula occludens-1 (Zo-1) staining with significant gap formation. Hypoxia increased gelatinolytic activity specifically in vascular structures and gel zymography identified MMP-9 as enzymatic source. Treatment with an MMP inhibitor reduced vascular leakage and attenuated disorganization of TJ. Inhibition of vascular endothelial growth factor (VEGF) attenuated vascular leakage and MMP-9 activation induced by hypoxia. In conclusion, our data suggest that hypoxia-induced edema formation is mediated by MMP-9-dependent TJ rearrangement by a mechanism involving VEGF. Therefore, inhibition of MMP-9 might provide the basis for therapeutic strategies to treat brain edema. [ABSTRACT FROM AUTHOR]

The effects of freeze-thaw, freezing and sediment geochemistry on terminal anaerobic processes occurring in sediments taken from below cyanobacterial mats in meltwater ponds of the McMurdo Ice Shelf in Antarctica were investigated. Depending on the geochemical and physical status of the sediments (i.e., frozen or thawed), as well as passage of sediment through a freeze-thaw cycle, terminal carbon and electron flow shifted in which the proportions of hydrogen and acetate utilized for methanogenesis and sulfate reduction changed. Thus, in low-sulfate (or chloride) sediment which was thawed and incubated at 4°C, total carbon and electron flow were mediated by acetate-driven sulfate reduction and H[sub 2]-driven methanogenesis. When the same sediments were incubated frozen, both methanogenesis and sulfate reduction decreased. However, under these conditions methanogenesis was favored over sulfate reduction, and carbon flow from acetate to methane increased relative to sulfate reduction; > 70% of methane was contributed by acetate, and more than 80% of acetate was oxidized by pathways not coupled to sulfate reduction. In high-sulfate pond sediments, sulfate reduction was a major process mediating terminal carbon and electron flow in both unfrozen and frozen incubations. However, as with low-sulfate sediments, acetate oxidation became uncoupled from sulfate reduction with freezing. Geochemical and temperature effects could be expressed by linear models in which the log (methanogenesis to sulfate reduction) was negative log linear with respect to either temperature or the log of the sulfate (or chloride) concentration. From these relationships it was possible to predict the ratio for a given temperature (low-sulfate sediments) or sulfate (chloride) concentration. Small transitory changes, such as elevated sulfate reduction coupled to increased acetate turnover, resulted from application of a freeze-thaw cycle to low-salinity pond sediments. The results demonstrate... [ABSTRACT FROM AUTHOR]

Describes the major heterothrophic processes occurring in the sediments of a low-salinity melt-water pond in Antarctica. Effect of acetate addition on methanogenesis; Methane production stimulated by formate; Inhibition of methanogenesis by chloride.

Since no previous randomized comparison has been carried out between ultra-high and conventional dosage streptokinase therapy of fresh venous thromboses, the NBVL trial was carried out as a prospective, randomized, multicentre, phlebographically monitored comparison of the results and adverse effects of these two fibrinolytic treatment options. Using the normal exclusion criteria, 156 patients with a leg–pelvis venous thrombosis presumed to be a maximum of 14 days old were treated with 1.5 million U streptokinase/h for 6h daily ( n= 77, group A) or conventional dosage with 100 000 U streptokinase per hour ( n= 79, group B). There were 15 patients (eight in group A, seven in group B) who had to stop therapy prematurely, and eight patients (five in group A, three in group B) could not be evaluated because of incorrect monitoring times. The phlebograms were evaluated using IFP-C scores. These showed a reduction in the IFP score from 4.55 to 2.2 in the 64 patients in group A after a mean of 2.7 ± 0.6 therapy cycles with administration of 24.4 ± 5.7 million U streptokinase, i.e. 47% of the baseline value. The 69 patients in group B had a reduction in score from 4.2 to 2.93 after a mean of 3.7 ± 1.2 days of treatment with administration of 8.6 ± 3.3 million units, i.e. a fall of 30% in the baseline values ( p= 0.007). There were 132 out of 281 completely occluded venous segments in group A (47%) and 81 out of 279 segments in group B (29%) that showed complete patency. Eight out of 27 three-segment occlusions in group A and only one of 26 in group B showed complete patency. The IFP score improved by 55% in the 45 men in group A, compared with only 30% in the 47 men in group B ( p= 0.002). When both dosages are combined, men showed a greater improvement in IFP score than women (42 versus 29%; p= 0.02). The IFP score improved more in the 20 patients aged more than 60 years in group A than in the 19 patients aged over 60 years of age in group B (61 versus 20%; p= 0.003). No other significant differences in effect were seen on analysis of sub-groups and individual factors (sex, age, presumed age of thrombus and side of thrombosis). In the 77 patients in group A, haemorrhagic complications were less frequent than in the 79 patients in group B (22.1 versus 36.7%; p= 0.054), especially concerning urogenital haemorrhage (6.5 versus 22.8%; p= 0.004). Women were affected more frequently by haemorrhagic complications than men (35.2 versus 26.5%), and the 19 patients aged more than 65 years old were affected more than the 137 younger patients (21.1 versus 13.9%). There were no deaths, and clinically insignificant pulmonary emboli occurred three times. Ultra-high dosage streptokinase shows better and more rapid thrombolytic treatment for popliteal–femoral–iliac venous thromboses and causes fewer haemorrhagic complications than conventional dosage streptokinase. The better effect of ultra-high dosage can be observed particularly for three-segment occlusion as well as in male patients. In older patients, accurate diagnosis is required because of the higher rate of haemorrhagic complications. [ABSTRACT FROM AUTHOR]

High spatial resolution mass spectrometry imaging has been identified as a key technology needed to improve understanding of the chemical components that influence antibiotic resistance within biofilms, which are communities of micro-organisms that grow attached to a surface. Time-of-flight secondary ion mass spectrometry (ToF–SIMS) offers the unique ability for label-free 3D imaging of organic molecules with sub-micrometer spatial resolution and high sensitivity. Several studies of biofilms have been done with the help of ToF–SIMS, but none of those studies have shown 3D imaging of antibiotics in native-state hydrated biofilms with cell-level resolution. Because ToF–SIMS measurements must be performed in a high-vacuum environment, cryogenic preparation and analysis are necessary to preserve the native biofilm structure and antibiotic spatial distribution during ToF–SIMS measurements. In this study, we have investigated the penetration of the antibiotic ciprofloxacin into Bacillus subtilis biofilms using sub-micrometer resolution 3D imaging cryo-ToF–SIMS. B. subtilis biofilms were exposed to physiologically relevant levels of ciprofloxacin. The treated biofilms were then plunge-frozen in liquid propane and analyzed with ToF–SIMS under cryogenic conditions. Multivariate analysis techniques, including multivariate curve resolution (MCR) and inverse maximum signal factor (iMSF) denoising, were used to aid analysis of the data and facilitate high spatial resolution 3D imaging of the biofilm, providing individually resolved cells and spatially resolved ciprofloxacin intensity at "real world" concentrations. [ABSTRACT FROM AUTHOR]

Aquaculture is a global-scale industry providing sustainable production of protein-rich foods required to feed the growing world population. Microalgae cultivation in aquaculture bioreactors can exude extracellular polymeric substances leading to biofouling of culture infrastructure and increased algal disease risk. A structure–behaviour relationship was developed by examining how the surface wettability of a range of functional nanocoatings impacts the extent of biofouling during exposure to continuous microalgae culture under normal hydrodynamic conditions. High-wetting (hydrophilic) surfaces were found to reduce biofouling better than water-repelling (hydrophobic) surfaces. Low toxicity in conjunction with antifouling behaviour was found for pulsed plasma poly(4-vinylpyridine) coated bioreactor surfaces (water contact angle = 38 ± 5°) towards the marine microalgal species Chaetoceros calcitrans, Chaetoceros mulleri , and Tisochrysis lutea (T- Iso), which are commonly grown as aquaculture food. [Display omitted] • Nanocoatings are fabricated with varying surface wetting. • A structure–behaviour relationship correlates surface wetting to extent of biofouling during microalgae culture exposure. • High wetting (hydrophilic) surfaces are better at reducing biofouling compared to water repelling (hydrophobic) surfaces. • Most effective are non-toxic pulsed plasma poly(4-vinylpyridine) nanocoatings. [ABSTRACT FROM AUTHOR]

Abstract: In the brain, glucose is transported by GLUT1 across the blood–brain barrier and into astrocytes, and by GLUT3 into neurons. In the present study, the expression of GLUT1 and GLUT3 mRNA and protein was determined in adult neural stem cells cultured from the subventricular zone of rats. Both mRNAs and proteins were coexpressed, GLUT1 protein being 5-fold higher than GLUT3. Stress induced by hypoxia and/or hyperglycemia increased the expression of GLUT1 and GLUT3 mRNA and of GLUT3 protein. It is concluded that adult neural stem cells can transport glucose by GLUT1 and GLUT3 and can regulate their glucose transporter densities. [Copyright &y& Elsevier]

The article introduces a possible chemical separation of a mixture of two compounds on the metal nanorods surface. A silver nanorods surface has been prepared by controlled electrochemical deposition in anodic alumina oxide (AAO) template. Rhodamine 6G and 4-aminothiophenol have been directly applied to the sampling point on a silver nanorods surface in an aliquot mixture. The position of the resolved compounds was analysed by time-of-flight secondary ion mass spectrometry (TOF-SIMS) which measured the fragments and the molecular ions of the two compounds separated on the silver nanorods surface. Rhodamine 6G has been preconcentrated as 1.5 mm radial from the sampling point while 4-aminothiophenol formed a continuous self-assembled monolayer on the silver nanorods surface with a maximum molecular ion intensity at a distance of 0.5 mm from the sampling point. The separation of the single chemical components from the two-component mixture over the examined silver nanostructured films could clearly be shown. A fast separation on the mentioned nanotextured films was observed (within 50 s). This procedure can be easily integrated into the micro/nanofluidic systems or chips and different detection systems can be applied. [ABSTRACT FROM AUTHOR]

Zoned phenocrysts in volcanic rocks potentially provide an archive of magmatic processes. As a crystal grows and comes into contact with different melt batches, the chemical and textural signature of this journey is recorded within its crystal lattice. The timescale of some magmatic processes can be investigated through the relaxation of chemical gradients across crystal growth zones through the application of diffusion modeling techniques. One of the current limitations to diffusion modeling is the spatial and analytical resolution of the chemical profile that conventional techniques such as electron probe microanalyzer (EPMA), dynamic secondary ion mass spectrometry (SIMS), and laser ablation-inductively coupled plasma mass spectrometry (LA-ICPMS) can achieve. Here, for the first time, we present time-of-flight (TOF) SIMS (TOF-SIMS) data for zoning of orthopyroxene crystals from the May 1982 eruption of Mount St. Helens volcano, U.S.A., and cross-calibrate these data between backscattered electron images and EPMA. TOF-SIMS has the advantage of being able to achieve micrometer to nanoscale spatial resolution of major elements as well as analyses of light elements, such as Li, and trace and minor elements (Na, K, and Ni) at concentrations that cannot be achieved by EPMA, provided that convolution (overlap) effects and polyatomic mass inferences are carefully considered. With TOF-SIMS analyses we identified zoning of Li on a spatial scale (ca. 5--10 µm) that would be inaccessible to most other conventional analytical techniques. Preliminary results indicate that Li, a fast-diffusing element, may be introduced to the crystals in the minutes, hours, or days prior to eruption and may provide insights into pre-eruptive magmatic processes. Thus, TOF-SIMS has the potential to be a powerful tool for obtaining minor and trace element profiles across compositional interfaces within crystals at high-spatial resolution. [ABSTRACT FROM AUTHOR]

Abstract: In this work, polyethyleneglycole (PEG) is introduced into polypyrrole (PPy) film coated on LiFePO4 powder particles to promote the properties of cathode material for lithium-ion batteries. The enhancement of the electrochemical activity by the substitution of a carbon with electrochemically active polymer is investigated. Films of the PPy doped with the PEG were prepared by the chemical oxidative polymerization of pyrrole (Py) monomer. PEG has been added as an additive during polymerization process to improve mechanical and structural properties of the PPy in final PPy/PEG–LiFePO4 cathode material. Cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and galvanostatic charge/discharge measurements were employed to characterize the electrochemical properties of PPy/PEG–LiFePO4 material. The electrochemical performance of PPy–LiFePO4 electrodes was greatly improved by introduction of PEG into the PPy films. Charge/discharge measurements confirmed the increase in capacity when applying PEG in PPy. The morphology and particle sizes of the prepared cathode powder material were investigated by scanning electron microscopy (SEM) and particle size analysis (PSA). Distribution of PPy and PPy/PEG films onto the LiFePO4 particles surface was studied by time of flight secondary ion mass spectrometry (TOF-SIMS). In addition to polymeric coating layer on the surface of PPy–LiFePO4 composite particles, some PPy unequally distributed between the particles was found. The median diameter value is 4.92μm for PPy–LiFePO4 sample. TOF-SIMS measurements and SEM images confirmed that thickness of polypyrrole coating on LiFePO4 particles is about 100nm. [Copyright &y& Elsevier]

Recent publications on static secondary ion mass spectrometry (S-SIMS) focus on molecular depth profiling by using polyatomic or ultra-low energy monoatomic projectiles. Since their applicability depends on the relationship between the ion yield and the depth, which is hard to obtain without extensive studies, a combination of a wear test method with S-SIMS surface analysis was performed in the current study. Using this non-sputtering procedure, the relation between the signal intensity and the local concentration remains in principle the same as that at the surface (which is easy to determine). Mechanical erosion was successfully applied to expose sub-surface material from organic multilayers. Through surface analysis with S-SIMS on the gradually exposed deeper planes, molecular depth profiles could be obtained. The study was conducted on a model system relevant to offset printing, consisting of two polymer layers, containing dyes and a surfactant, cast on an Al substrate. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Abstract: Boron Neutron Capture Therapy (BNCT) is based on the ability of the stable isotope 10B to capture neutrons, which leads to a nuclear reaction producing an alpha- and a 7Li-particle, both having a high biological effectiveness and a very short range in tissue, being limited to approximately one cell diameter. This opens the possibility for a highly selective cancer therapy. BNCT strongly depends on the selective uptake of 10B in tumor cells and on its distribution inside the cells. The chemical properties of boron and the need to discriminate different isotopes make the investigation of the concentration and distribution of 10B a challenging task. The most advanced techniques to measure and image boron are described, both invasive and non-invasive. The most promising approach for further investigation will be the complementary use of the different techniques to obtain the information that is mandatory for the future of this innovative treatment modality. [Copyright &y& Elsevier]

Objective: Mesenchymal stem cells (MSC) raise high hopes in clinical applications. However, the lack of common standards and a precise definition of MSC preparations remains a major obstacle in research and application of MSC. Whereas surface antigen markers have failed to precisely define this population, a combination of proteomic data and microarray data provides a new dimension for the definition of MSC preparations. Methods: In our continuing effort to characterize MSC, we have analyzed the differential transcriptome and proteome expression profiles of MSC preparations isolated from human bone marrow under two different expansion media (BM-MSC-M1 and BM-MSC-M2). Results: In proteomics, 136 protein spots were unambiguously identified by MALDI-TOF-MS and corresponding cDNA spots were selected on our “Human Transcriptome cDNA Microarray.” Combination of datasets revealed a correlation in differential gene expression and protein expression of BM-MSC-M1 vs BM-MSC-M2. Genes involved in metabolism were more highly expressed in BM-MSC-M1, whereas genes involved in development, morphogenesis, extracellular matrix, and differentiation were more highly expressed in BM-MSC-M2. Interchanging culture conditions for 8 days revealed that differential expression was retained in several genes whereas it was altered in others. Conclusion: Our results have provided evidence that homogeneous BM-MSC preparations can reproducibly be isolated under standardized conditions, whereas culture conditions exert a prominent impact on transcriptome, proteome, and cellular organization of BM-MSC. [Copyright &y& Elsevier]

Simple Summary: Breast cancer is the second most common diagnosed malignancy in women worldwide. In this study, we examine the feasibility of breast tumor characterization based on [18F]FDG-PET/CT images using machine learning (ML) approaches in combination with data-preprocessing techniques. ML prediction models for breast cancer detection and the identification of breast cancer receptor status, proliferation rate, and molecular subtypes were established and evaluated. Furthermore, the importance of most repeatable features was investigated. Results displayed high performance of malignant/benign tumor differentiation and triple negative tumor subtype ML models. We observed high repeatability of radiomic features for both high performing predictive models. Background: This study investigated the performance of ensemble learning holomic models for the detection of breast cancer, receptor status, proliferation rate, and molecular subtypes from [18F]FDG-PET/CT images with and without incorporating data pre-processing algorithms. Additionally, machine learning (ML) models were compared with conventional data analysis using standard uptake value lesion classification. Methods: A cohort of 170 patients with 173 breast cancer tumors (132 malignant, 38 benign) was examined with [18F]FDG-PET/CT. Breast tumors were segmented and radiomic features were extracted following the imaging biomarker standardization initiative (IBSI) guidelines combined with optimized feature extraction. Ensemble learning including five supervised ML algorithms was utilized in a 100-fold Monte Carlo (MC) cross-validation scheme. Data pre-processing methods were incorporated prior to machine learning, including outlier and borderline noisy sample detection, feature selection, and class imbalance correction. Feature importance in each model was assessed by calculating feature occurrence by the R-squared method across MC folds. Results: Cross validation demonstrated high performance of the cancer detection model (80% sensitivity, 78% specificity, 80% accuracy, 0.81 area under the curve (AUC)), and of the triple negative tumor identification model (85% sensitivity, 78% specificity, 82% accuracy, 0.82 AUC). The individual receptor status and luminal A/B subtype models yielded low performance (0.46–0.68 AUC). SUVmax model yielded 0.76 AUC in cancer detection and 0.70 AUC in predicting triple negative subtype. Conclusions: Predictive models based on [18F]FDG-PET/CT images in combination with advanced data pre-processing steps aid in breast cancer diagnosis and in ML-based prediction of the aggressive triple negative breast cancer subtype. [ABSTRACT FROM AUTHOR]

Here, we show the localization of a whole organic molecule in biological tissue using time-of-flight secondary ion mass spectrometry (TOF-SIMS).Rat kidneys were sectioned by cryoultramicrotomy and dried at room temperature. The samples were covered with a thin silver layer and analyzed in an imaging TOF-SIMS instrument equipped with a Ga+-source. The cholesterol signal showed a high concentration in the nuclear areas of the epithelial cells and a lower concentration over areas representing the basal lamina of renal tubules. A more diffuse distribution of cholesterol was also found over areas representing the cytoplasm or plasma membrane of the epithelial cells. [Copyright &y& Elsevier]

Summary Cholesterol is an essential component of most biological membranes and serves important functions in controlling membrane integrity, organization, and signaling. However, probes to follow the dynamic distribution of cholesterol in live cells are scarce and so far show only limited applicability. Herein, we addressed this problem by synthesizing and characterizing a class of versatile and clickable cholesterol-based imidazolium salts. We show that these cholesterol analogs faithfully mimic the biophysical properties of natural cholesterol in phospholipid mono- and bilayers, and that they integrate into the plasma membrane of cultured and primary human cells. The membrane-incorporated cholesterol analogs can be specifically labeled by click chemistry and visualized in live-cell imaging experiments that show a distribution and behavior comparable with that of endogenous membrane cholesterol. These results indicate that the cholesterol analogs can be used to reveal the dynamic distribution of cholesterol in live cells. [ABSTRACT FROM AUTHOR]