Dysregulated CD38 Expression on Peripheral Blood Immune Cell Subsets in SLE

Given its uniformly high expression on plasma cells, CD38 has been considered as a therapeutic target in patients with systemic lupus erythematosus (SLE). Herein, we investigate the distribution of CD38 expression by peripheral blood leukocyte lineages to evaluate the potential therapeutic effect of CD38-targeting antibodies on these immune cell subsets and to delineate the use of CD38 as a biomarker in SLE. We analyzed the expression of CD38 on peripheral blood leukocyte subsets by flow and mass cytometry in two different cohorts, comprising a total of 56 SLE patients. The CD38 expression levels were subsequently correlated across immune cell lineages and subsets, and with clinical and serologic disease parameters of SLE. Compared to healthy controls (HC), CD38 expression levels in SLE were significantly increased on circulating plasmacytoid dendritic cells, CD14⁺⁺CD16⁺ monocytes, CD56⁺ CD16^dim natural killer cells, marginal zone-like IgD⁺CD27⁺ B cells, and on CD4⁺ and CD8⁺ memory T cells. Correlation analyses revealed coordinated CD38 expression between individual innate and memory T cell subsets in SLE but not HC. However, CD38 expression levels were heterogeneous across patients, and no correlation was found between CD38 expression on immune cell subsets and the disease activity index SLEDAI-2K or established serologic and immunological markers of disease activity. In conclusion, we identified widespread changes in CD38 expression on SLE immune cells that highly correlated over different leukocyte subsets within individual patients, but was heterogenous within the population of SLE patients, regardless of disease severity or clinical manifestations. As anti-CD38 treatment is being investigated in SLE, our results may have important implications for the personalized targeting of pathogenic leukocytes by anti-CD38 monoclonal antibodies.     

Hydrotropic properties of some short-chain alkylbenzene- and alkylnaphthalene sulfonates

Alkylbenzene sulfonates based on toluene, xylene and cumene, and alkylnaphthalene sulfonates act as hydrotropes in surfactant systems. One measure of hydrotropicity is the amount of hydrotrope required to clear a cloudy detergent formulation; some hydrotropes are more effective than others, depending on the surfactant formulation. Another measure is the modification of the viscosity of surfactant formulations; the change in the viscosity depends on the amount and type of hydrotrope used and on the specific formulation involved. Additionally, alkylnaphthalene sulfonate hydrotropes change the solubility of nonionic surfactants in water, and both types of hydrotrope raise the cloud point of nonionic surfactant solutions; however, the naphthalene-based hydrotropes are more efficient. Ross-Miles foam test data are used to compare the foam characteristics of different alkylnaphthalene sulfonates. A critical micelle concentration (CMC) was determined for the alkylnaphthalene sulfonates, but although alkylbenzene sulfonates do show some surface activity, a CMC could not be found for these materials. Presented as a poster session at the AOCS Annual Meeting & Expo, May 1997, Seattle, Washington, and at Soaps, Detergents, and Oleochemicals: An AOCS International Conference, October 1997, Fort Lauderdale, Florida.     

Establishing Environmental Water Requirements for the Murray–Darling Basin,Australia's Largest Developed River System

There is a global need for management of river flows to be informed by science to protect and restore biodiversity and ecological function while maintaining water supply for human needs. However, a lack of data at large scales presents a substantial challenge to developing a scientifically robust approach to flow management that can be applied at a basin and valley scale. In most large systems, only a small number of aquatic ecosystems have been well enough studied to reliably describe their environmental water requirements. The umbrella environmental asset (UEA) approach uses environmental water requirements developed for information‐rich areas to represent the water requirements of a broader river reach or valley. We illustrate this approach in the Murray–Darling Basin (MDB) in eastern Australia, which was recently subject to a substantial revision of water management arrangements. The MDB is more than 1 million km² with 18 main river valleys and many thousands of aquatic ecosystems. Detailed eco‐hydrologic assessments of environmental water requirements that focused on the overbank, bankfull and fresh components of the flow regime were undertaken at a total of 24 UEA sites across the MDB. Flow needs (e.g. flow magnitude, duration, frequency and timing) were established for each UEA to meet the needs of key ecosystem components (e.g. vegetation, birds and fish). Those flow needs were then combined with other analyses to determine sustainable diversion limits across the basin. The UEA approach to identifying environmental water requirements is a robust, science‐based and fit‐for‐purpose approach to determining water requirements for large river basins in the absence of complete ecological knowledge. © 2015 The Authors. River Research and Applications published by John Wiley & Sons, Ltd.     

Resolving the origin of the petrogenic hydrocarbon background in Prince William Sound, Alaska

The dominant sources of the petrogenic hydrocarbon background in benthic sediments of Prince William Sound, AK (PWS), site of the 1989 Exxon-Valdez oil spill, are eroding Tertiary shales and residues of natural oil seepage. Mass balance considerations and statistical analyses of hydrocarbon fingerprints independently indicate that coal contributes generally less than 1% of the polycyclic aromatic hydrocarbons (PAH) and chemical biomarkers in this background. This is environmentally significant because of presumed differences in the bioavailability of PAH in coal, seep oil residues, and shales. Coal particles are present in PWS sediments, but their PAH and chemical biomarker contributions are overwhelmed by those of seep oil residues and organic particles from shales of low-to-high thermally maturity. In the late Tertiary or early Quaternary, the currently exposed and eroding shale formations were heated into the oil-generation window and, consequently, are now relatively rich in extractable PAH and chemical biomarkers. The exposed and eroding coals in the area, in contrast, experienced long hot burial and are now thermally overmature with respect to oil generation. The concentrations of thermally sensitive PAH and biomarker compounds in PWS sediments are not consistent with a mature coal origin but are consistent with the low-to-high maturity shales and seep oils in the area.     

Assessing terrestrial wildlife populations in the Toronto and Region Area of Concern

Beneficial use impairments (BUIs) under the Great Lakes Water Quality Agreement identify environmental issues requiring remedial action within the Great Lakes Areas of Concern (AOCs). We conducted this study to support the assessment of the wildlife component of BUI 3: degradation of fish and wildlife populations. We compared bird and amphibian (frogs and toads) data from the Toronto and Region Conservation Authority’s Terrestrial Long-term Monitoring Program in the Toronto and Region AOC to an adjacent, but otherwise similar, reference watershed, Duffins Creek. Twelve of 13 targets were met within the AOC for forest bird, wetland bird, meadow bird and amphibian populations based on averages of mean annual values at sites within the AOC that were within two standard deviations of averages at sites in the Duffins Creek reference watershed between 2008 and 2017. Even though wildlife populations within the AOC were within the normal range of variability expected from a reference watershed, they were often at lower levels than within the Duffins Creek reference watershed. In addition, forest bird and amphibian populations were negatively affected by urbanization within the AOC and meadow bird indices declined. We conclude that while wildlife populations within the AOC currently meet targets for BUI 3, they continue to be negatively impacted by numerous stressors that are primarily related to past and ongoing urbanization. Thus, continued restoration of wildlife habitat and protection of existing habitat within the AOC is highly recommended.     

Novel Solid‐State Microbial Sensors Based on ZnO Nanorod Arrays

Gravity and magnetism are implemented to change the morphology of zinc oxide nanorod sensors during synthesis. The effects of gravity and magnetism can translate into future application of these nanorods through cost‐effective, environmentally friendly, and easy‐to‐use biosensor technology with the quickest available sensing. The sensors can pave the way toward detection of both bacteria and fungi present on the surface with high sensitivity. This ability to sense microorganisms in a “non‐solution‐based” environment represents a key step forward in the fields of health and food safety, as well as solid‐state nanomaterial biotechnology applications. Hundreds of thousands of people are affected each year by accidental contamination and current protocols are far from preventative. The results of the magnetic field studies when compared with previous results show that the following factors affect the outcome of applying magnetic field during the growth of nanorods on their morphology: the direction of growth with respect to gravity, the method of seeding, and the substrate.     

Viscous dissipation and apparent wall slip in capillary rheometry of ice cream

We have analysed sets of capillary rheometry data (0.3 s^?1 ≤ γ_app ≤ 360 s^?1) for a commercial ice cream as it flowed from a freezer on an industrial flow line. Pressure drop measurements were used and particular attention was paid to viscous dissipation effects. A semi-analytical model presented by Bird in 1955 indicated that over one third of the data points were subject to local wall heating, which was consistent with available temperature measurements. The filtered data were used to construct a viscosity function which, when implemented in a detailed CFD simulation of the flow, predicted the observed flow curve behaviour. The results demonstrate that viscous dissipation can be significant in ice cream and that interpretation of this behaviour in terms of wall slip is erroneous.     

Defective repair of oxidative damage in mitochondrial DNA in Down''s syndrome

BACKGROUND: Synthetic homopyrimidine peptide nucleic acids (PNAs) can bind complementary targets in double-stranded DNA, generating strand-displacement complexes, and so offering an opportunity to modulate specific gene expression. Several issues remain to be addressed before these attributes can be exploited in vivo, however. RESULTS: The kinetics of the interaction between a homopyrimidine PNA and a complementary homopurine target on double-stranded DNA were analyzed in the presence or absence of a preformed strand-displacement complex proximal to the target. The complex was established under low salt conditions by the binding of a different homopyrimidine PNA to a target situated adjacent to the first PNA target. These two targets were placed next to each other on opposite strands at distances of 0, 2, 4 and 8 base pairs apart. The presence of a preformed strand-displacement complex near the target accelerates the binding of PNA to double-stranded DNA in a salt-dependent manner. The influence of salt on the binding rates was also examined. The binding rate is increased by a factor of 1 x exp(70[NaCl]), that is, 16-fold at 40 mM NaCl and more than 10(4)-fold if extrapolated to 140 mM NaCl. This effect is significantly reduced if the two targets are 2 base pairs apart and completely absent if the distance is 4 base pairs or more. CONCLUSIONS: The perturbation of the DNA helix imposed by a PNA strand-displacement complex only propagates a few base pairs. It is therefore possible to target sites in the immediate vicinity of strand invasion complexes specifically. The results presented have implications for the mechanism of strand displacement and for the application of PNA in a genomic context.