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.     

Refining Genotypes and Phenotypes in KCNA2-Related Neurological Disorders

Pathogenic variants in KCNA2, encoding for the voltage-gated potassium channel K_v1.2, have been identified as the cause for an evolving spectrum of neurological disorders. Affected individuals show early-onset developmental and epileptic encephalopathy, intellectual disability, and movement disorders resulting from cerebellar dysfunction. In addition, individuals with a milder course of epilepsy, complicated hereditary spastic paraplegia, and episodic ataxia have been reported. By analyzing phenotypic, functional, and genetic data from published reports and novel cases, we refine and further delineate phenotypic as well as functional subgroups of KCNA2-associated disorders. Carriers of variants, leading to complex and mixed channel dysfunction that are associated with a gain- and loss-of-potassium conductance, more often show early developmental abnormalities and an earlier onset of epilepsy compared to individuals with variants resulting in loss- or gain-of-function. We describe seven additional individuals harboring three known and the novel KCNA2 variants p.(Pro407Ala) and p.(Tyr417Cys). The location of variants reported here highlights the importance of the proline(405)–valine(406)–proline(407) (PVP) motif in transmembrane domain S6 as a mutational hotspot. A novel case of self-limited infantile seizures suggests a continuous clinical spectrum of KCNA2-related disorders. Our study provides further insights into the clinical spectrum, genotype–phenotype correlation, variability, and predicted functional impact of KCNA2 variants.     

Some aspects of the role of coal thermoplasticity and coke structure in coal gasification. 2. The effects of pressure and heating rate on dilatometric parameters and optical anisotropy development

An examination of the influence of pressure and heating rate on the thermoplastic properties of a weakly coking coal and of coal with various pitch-like additives was carried out using a high pressure dilatometer. Pressure up to 4 MPa markedly increased the swelling properties and increased the plastic range by decreasing the softening temperature, but the effects of pressure were strongly influenced by rate of heating with high heating rates enhancing the effects. Additions of tar or pitch also enhanced swelling at low pressure. The solid carbonization residues from the dilatometer were examined by polarized light microscopy to determine the content and composition of optically anisotropic species. The anisotropic content was increased by increases in pressure and heating rate and pitch additives enhanced the anisotropic content, especially at low pressure, without affecting the composition of the anisotropy. No direct correlations exist between the dilatometric parameters and the optical anisotropy but their dependence on the conditions emphasizes that when considering high pressure gasification of coal, it is necessary to obtain data under appropriate conditions.     

The ageing Australian firefighter: an argument for age-based recruitment and fitness standards for urban fire services

Currently, there is no enforcement of physical standards within Australian fire services post-recruitment, possibly leading to inappropriate fitness and body composition. This study evaluated the impacts of ageing on physical standards of Australian firefighters. Seventy-three firefighters from three different 10-year age groups [25–34 years (n = 27), 35–44 years (n = 27), 45–54 years (n = 19)] volunteered for physical testing using dual-energy X-ray analysis and existing fitness tests used for recruitment by an Australian fire service. Older (45–54 years) participants demonstrated significantly poorer physical standards compared with younger participants including cardiovascular fitness (p < 0.05), strength (p = 0.001) and simulated operational power testing tasks (p < 0.001). Age-related body composition changes were also observed independent of body mass index. Minimum recruitment standards and fitness programs need to account for age-related declines in physical capabilities to ensure that the minimum standard is maintained regardless of age.

Practitioner Summary: Using dual-energy X-ray analysis and established fitness testing protocols, this study aimed to gain an appreciation of the current standards of body composition and fitness of Australian firefighters and the effects of ageing on their physical abilities post-recruitment. The study demonstrated a significant decline in physical standards due to age.     

Partial oxidation of methane to methanol-comparison of heterogeneous catalyst and homogeneous gas phase reactions

Potential catalysts for the partial oxidation of methane to methanol have been synthesised and tested in high pressure annular reactors. Uranium oxide and molybdenum oxide catalysts and iron sodalite catalyst have been tested under the conditions reported in the patents and under conditions which allow comparison with reactions carried out in the gas phase. None of the catalysts tested showed an improvement on the gas phase results. It was found that the oxidative nature of the metal oxide catalysts is an inherent feature which reduces the selectivity to methanol.     

Desulphurization of coals and chars by treatment in various atmospheres between 400 and 600 °C

Desulphurization of fifteen US coals of rank ranging from anthracite to sub-bituminous B and five high-temperature chars by carbon monoxide and other gases and gas mixtures between 400 and 600 °C has been studied. The sulphur content of the parent coals ranged between 3.0 and 7.3% and that of the chars between 1.3 and 3.8% by weight. A comparison between air, nitrogen, carbon monoxide, and steam-carbon monoxide mixtures as desulphurizing gases shows the order of desulphurizing ability as

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Catalysis of gasification of coal-derived cokes and chars

Calcium is the most important in-situ catalyst for gasification of US coal chars in O₂, CO₂ and H₂O. It is a poor catalyst for gasification of chars by H₂. Potassium and sodium added to low-rank coals by ion exchange and high-rank coals by impregnation are excellent catalysts for char gasification in O₂, CO₂ and H₂O. Carbon monoxide inhibits catalysis of the CH₂O reaction by calcium, potassium and sodium; H₂ inhibits catalysis by calcium. Thus injection of synthesis gas into the gasifier will inhibit the CH₂O reaction. Iron is not an important catalyst for the gasification of chars in O₂, CO₂ and H₂O, because it is invariably in the oxidized state. Carbon monoxide disproportionates to deposit carbon from a dry synthesis gas mixture (3 vol H₂ + 1 vol CO) over potassium-, sodium- and iron-loaded lignite char and a raw bituminous coal char, high in pyrite, at 1123 K and 0.1 MPa pressure. The carbon is highly reactive, with the injection of 2.7 kPa H₂O to the synthesis gas resulting in net carbon gasification. The effect of traces of sulphur in the gas stream on catalysis of gasification or carbon-forming reactions by calcium, potassium, or sodium is not well understood at present. Traces of sulphur do, however, inhibit catalysis by iron.     

Abstracts

Journal of the American Oil Chemists' Society -