12 research outputs found
Impacts of some divalent cations on periplasmic nitrate reductase and dehydrogenase enzymes of Escherichia, Pseudomonas and Acinetobacter species
The impacts of Hg2+, Cd2+ and Zn2+ on the activities of periplasmic nitrate reductase (NAP) and dehydrogenase (DHA) enzymes of three organisms isolated from soil and sediment-water interface were analysed in liquid culture studies. NAP and DHA activities were estimated from nitrite and triphenyl formazan were produced respectively after 4h incubation at 28 ± 2oC. Hg2+ completely inhibited NAP activity in Escherichia and Pseudomonas spp at all the concentrations (0.2 – 1mM) while progressive inhibitions of NAP activity were observed in Escherichia and Pseudomonas spp with increasing concentrations of Zn2+ and Cd2+. Both metals were stimulatory to NAP of Acinetobacter sp at 0.2 – 1mM. Apart from stimulation of DHA activity by Zn2+ (0.2 – 1mM) in Escherichia sp, Cd2+ (0.4 -1.0mM) in Acinetobacter sp and (1.0mM) in Pseudomonas sp, all the metals progressively inhibited DHA activities in the three organisms. In Escherichia sp, the activities of the two enzymes were negatively correlated on exposure to Zn2+ (r = -0.91) and positively correlated (r = >0.90) on exposure to Cd2+ and Hg2+. Based on IC50 values of the metals for the DHA and NAP enzymes, the most resistant of the three organisms were Escherichia sp and Acinetobacter sp respectively. Quantitatively, NAP with its lower IC50 values than DHA was a more sensitive toxicity measure for Hg2+ in all the organisms. The sensitivity of microbial metabolic enzymes to the toxic effects of metals varies with the type of enzyme, metal and the microorganism involved
The Orphan C2orf40 Gene is a Neuroimmune Factor in Alzheimer's Disease.
Expression of the orphan C2orf40 gene is associated with the aggregation of the neurofibrillary tangle-protein tau in transgenic mice, tumor suppression, the induction of senescence in CNS, and the activation of microglia and peripheral mononuclear leukocytes. This gene also encodes several secreted pro- and anti-inflammatory neuropeptide-like cytokines, suggesting they might be implicated in the inflammatory component(s) of Alzheimer's disease (AD). Accordingly, we evaluated human AD and control brains for expression changes by RT-qPCR, Western blot, and histological changes by immunolabeling. RT-qPCR demonstrated increased cortical gene expression in AD. The molecular form of Ecrg4 detected in cortex was 8-10 kDa, which was shown previously to interact with the innate immunity receptor complex. Immunocytochemical studies showed intensely stained microglia and intravascular blood-borne monocytes within cerebral cortical white matter of AD patients. Staining was diminished within cortical neurons, except for prominent staining in neurofibrillary tangles. Choroid plexuses showed a decreasing trend. These findings support our hypothesis that c2orf40 participates in the neuroimmune response in AD
Superoxide dismutase protects against apoptosis and alveolar enlargement induced by ceramide
The molecular events leading to emphysema development include generation of oxidative stress and alveolar cell apoptosis. Oxidative stress upregulates ceramides, proapoptotic signaling sphingolipids that trigger further oxidative stress and alveolar space enlargement, as shown in an experimental model of emphysema due to VEGF blockade. As alveolar cell apoptosis and oxidative stress mutually interact to mediate alveolar destruction, we hypothesized that the oxidative stress generated by ceramide is required for its pathogenic effect on lung alveoli. To model the direct lung effects of ceramide, mice received ceramide intratracheally (Cer12:0 or Cer8:0; 1 mg/kg) or vehicle. Apoptosis was inhibited with a general caspase inhibitor. Ceramide augmentation shown to mimic levels found in human emphysema lungs increased oxidative stress, and decreased, independently of caspase activation, the lung superoxide dismutase activity at 48 h. In contrast to their wild-type littermates, transgenic mice overexpressing human Cu/Zn SOD were significantly protected from ceramide-induced superoxide production, apoptosis, and air space enlargement. Activation of lung acid sphingomyelinase in response to ceramide treatment was abolished in the Cu/Zn SOD transgenic mice. Since cigarette smoke-induced emphysema in mice is similarly ameliorated by the Cu/Zn SOD overexpression, we hypothesized that cigarette smoke may induce ceramides in the mouse lung. Utilizing tandem mass spectrometry, we documented increased lung ceramides in adult mice exposed to cigarette smoke for 4 wk. In conclusion, ceramide-induced superoxide accumulation in the lung may be a critical step in ceramide's proapoptotic effect in the lung. This work implicates excessive lung ceramides as amplifiers of lung injury through redox-dependent mechanisms
Clinical analysis of patients with primary and secondary extranodal natural killer/T‐cell lymphoma of central nervous system
Hydrocarbon maturation modeling of Paleocene to Lower Miocene source rocks in the Niger Delta Basin: implications for hydrocarbon generation
Genomic and transcriptomic correlates of immunotherapy response within the tumor microenvironment of leptomeningeal metastases
AbstractLeptomeningeal disease (LMD) is a devastating complication of solid tumor malignancies, with dire prognosis and no effective systemic treatment options. Over the past decade, the incidence of LMD has steadily increased due to therapeutics that have extended the survival of cancer patients, highlighting the need for new interventions. To examine the efficacy of immune checkpoint inhibitors (ICI) in patients with LMD, we completed two phase II clinical trials. Here, we investigate the cellular and molecular features underpinning observed patient trajectories in these trials by applying single-cell RNA and cell-free DNA profiling to longitudinal cerebrospinal fluid (CSF) draws from enrolled patients. We recover immune and malignant cell types in the CSF, characterize cell behavior changes following ICI, and identify genomic features associated with relevant clinical phenomena. Overall, our study describes the liquid LMD tumor microenvironment prior to and following ICI treatment and demonstrates clinical utility of cell-free and single-cell genomic measurements for LMD research.</jats:p