Project description:Polyhydroxyalkanoates (PHAs) are bio-based, biodegradable polyesters that can be produced from organic-rich waste streams using mixed microbial cultures. To maximize PHA production, mixed microbial cultures may be enriched for PHA-producing bacteria with a high storage capacity through the imposition of cyclic, aerobic feast-famine conditions in a sequencing batch reactor (SBR). Though enrichment SBRs have been extensively investigated a bulk solutions-level, little evidence at the proteome level is available to describe the observed SBR behavior to guide future SBR optimization strategies. As such, the purpose of this investigation was to characterize proteome dynamics of a mixed microbial culture in an SBR operated under aerobic feast-famine conditions using fermented dairy manure as the feedstock for PHA production. At the beginning of the SBR cycle, excess PHA precursors were provided to the mixed microbial culture (i.e., feast), after which followed a long duration devoid of exogenous substrate (i.e., famine). Two-dimensional electrophoresis was used to separate protein mixtures during a complete SBR cycle, and proteins of interest were identified.
Project description:After elevated and reduced incubation temperature during embryonic days (ED) 7-10 and 10-13 changes of gene expression were determined at ED 10, ED 13, and post-hatch at day (D) 35
Project description:After elevated and reduced incubation temperature during embryonic days (ED) 7-10 and 10-13 changes of gene expression were determined at ED 10, ED 13, and post-hatch at day (D) 35
Project description:Experimental design: 2 genotypes: PI- (resistant USDA Plant Introduction (PI459025B) line containing SBR Rpp4 resistance gene) & Cultivar Williams that does not have a known SBR resistance gene 2 treatments: Soybean rust (Phakopsora pachyrhizi) isolate Hawaii 94-1 & mock infection 3 replications 6 time points: 12, 24, 72, 144, 216 and 288 hours after inoculation TOTAL: 72 Affymetrix GeneChip(R) Soybean Genome Arrays Mock treatment: 0.01% Tween 20 Hawaii 94-1 treatment: 500,000 spores per ml in 0.01% Tween 20 ****[PLEXdb(http://www.plexdb.org) has submitted this series at GEO on behalf of the original contributor, Steve Whitham. The equivalent experiment is GM37 at PLEXdb.]
Project description:Adaptive immunity plays a key role in osteoporosis in type 2 diabetes mellitus (T2DM); eldecalcitol (ED-71) is a novel active vitamin D analog, but its specific immunological mechanisms in ameliorating diabetic osteoporosis has not been well defined. In a T2DM mouse model, ED-71 attenuated bone loss and marrow adiposity. Simultaneously, it rectified imbalanced glucose homeostasis and dyslipidemia, ameliorated pancreatic β-cell damage and hepatic glycolipid metabolism disorder. Subsequently, in T2DM mice injected with CD25, we observed that the beneficial effects of ED-71 mentioned earlier were partially contingent on the Treg subsets ratio. Mechanistically, ED-71 promoted the differentiation of CD4+ T cells into Treg subsets, facilitating Ca2+ influx and the expression of ORAI1 and STIM1, pivotal proteins in store-operated Ca2+ entry (SOCE). The SOCE inhibitor, 2-APB, partially attenuated the positive effects of ED-71 observed in the above results. Together, these findings unveil ED-71 regulates SOCE-mediated Treg cell differentiation, accomplishing the dual purpose of simultaneously ameliorating diabetic osteoporosis and glucolipid metabolic disorders.
Project description:Digoxin is a well-recognized cardiovascular medication; however, epidemiological investigations have associated its clinical application with an elevated risk of malignancy. To elucidate it, we discovered, for the first time, that therapeutic digoxin can facilitate tumor metastasis by acting as an inducer of immune checkpoints, including PD-1, PD-L1/2, CTLA-4, LAG-3, ICOS, TIM-3, and TIGIT, among others. The PD-1/PD-L1 axis plays a pivotal role. Digoxin upregulates PD-L1 production in cancer cells through multiple mechanisms, including digoxin-PKM2 interaction, liquid-liquid phase separation, and Na,K-ATPase degradation. Notably, endogenous digoxin (ED) was significantly upregulated in breast cancer, correlating with increased metastasis. When specific nanobodies (Nbs) were developed to functionally inhibit ED in vivo, pulmonary tumor metastasis was reduced. However, the efficacy of ED-targeting Nbs was limited by endogenous ouabain (EO), another hormone structurally similar to digoxin. To address this, Nbs co-targeting ED and EO demonstrated an increased anti-metastatic effect and a notable reduction in immune checkpoint expression. Furthermore, Nbs simultaneously targeting ED, EO, and PD-1 exhibited significant synergy in suppressing tumor progression with a favorable safety profile. In conclusion, therapeutic digoxin and ED are potent inducers of immune checkpoints. Engineered nanobodies co-targeting cardiotonic hormones (ED, EO) and immune checkpoints present a promising novel approach in the treatment of breast cancer metastasis.