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Abstract Background Early seed germination in crops can confer a competitive advantage against weeds and reduce the time to maturation and harvest. WRKY transcription factors regulate many aspects of plant development including seed dormancy and germination. Both positive and negative regulators of seed germination have been reported in many plants such as rice and Arabidopsis. Using a transient expression system, we previously demonstrated that OsWRKY71 is a negative regulator of gibberellin (GA) signaling in aleurone cells and likely forms a “repressosome” complex with other transcriptional repressors. Hence, it has the potential to impact seed germination properties. Results In this study, we demonstrate that OsWRKY71, a Group IIa WRKY gene, appeared at the same time as seed-bearing plants. Rice mutants lacking OsWRKY71 have seeds and embryos that germinate earlier than wildtype controls. In oswrky71 aleurone layers, α-amylase activity was hypersensitive to stimulation by GA3 and hyposensitive to inhibition by abscisic acid (ABA). Early germination in oswrky71 intact seeds was also hyposensitive to ABA. Transcriptomic profiling during embryo germination and early post-germination growth demonstrates that OsWRKY71 influences the expression of 9–17% of genes in dry and imbibing embryos. Compared to wildtype embryos, the mutant transcriptomes have large temporal shifts at 4, 8 and 12 h after imbibition (HAI). Importantly, many genes involved in the ABA-dependent inhibition of seed germination were downregulated in oswrky71-1. This mutant also displayed altered expression of multiple ABA receptors (OsPYLs/RCARs) that control ABA signaling and the VP1-SDR4-DOG1L branch of ABA signaling that promotes seed dormancy. Association studies reveal an OsWRKY71-containing quantitative trait locus involved in low-temperature seed germinability, qLTG-2. Indeed, oswrky71 seeds germinated early at 15 °C. Conclusions Rice Group-IIa WRKY transcription factor OsWRKY71 is a master regulator of germination that influences the expression of 9–17% of genes in dry and imbibing embryos. It is also most likely the primary candidate of low-temperature seed germinability QTL, qLTG-2. We propose that knockouts of OsWRKY71 can generate rice varieties with improved germination properties under normal or low-temperature conditions.

Abstract Idecabtagene vicleucel (Ide-cel) has demonstrated excellent efficacy and durable responses in patients with relapsed/refractory multiple myeloma (RRMM). However, the outcomes with ide-cel in patients with extramedullary disease (EMD) remain incompletely characterized. We included patients with RRMM treated with ide-cel between May 2021 and April 2023 across 11 US academic institutions. Visceral or soft tissue lesions non-contiguous from bone was classified as EMD. Time-to-event analyses were performed from date of ide-cel infusion. Among 351 patients, 84 (24%) had EMD prior to infusion. The median follow-up from ide-cel infusion was 18.2 months (95% CI: 17-19.3). The day 90 overall response rates (ORR) were 52% vs. 82% for the EMD and non-EMD cohorts, respectively (p

Abstract The presence of extramedullary disease (EMD) has been associated with poor outcomes in patients with relapsed-refractory multiple myeloma (RRMM). Herein, we report the outcomes of RRMM patients who were treated with standard-of-care (SOC) chimeric antigen receptor (CAR) T-cell therapy and had active extraosseous EMD before the infusion. Data were retrospectively collected from patients at three US institutions with the intent to receive SOC CAR T. Responses were assessed per the International Myeloma Working Group criteria. A total of 152 patients proceeded with infusion, of whom 47 (31%) had EMD (EMD group) and 105 (69%) did not (non-EMD group). Baseline patient characteristics were comparable between the two groups. The EMD group had a higher incidence of high-grade CRS, steroid and anakinra use, and thrombocytopenia on day +30 compared to the non-EMD group. In addition, the EMD group had an inferior overall response rate (58% vs 96%, p

Abstract Most patients with multiple myeloma experience disease relapse after treatment with a B-cell maturation antigen-targeted therapy (BCMA-TT), and data describing outcomes for patients treated with sequential BCMA-TT are limited. We analyzed clinical outcomes for patients infused with standard-of-care idecabtagene vicleucel, an anti-BCMA chimeric antigen receptor (CAR) T-cell therapy, at 11 US medical centers. A total of 50 patients with prior BCMA-TT exposure (38 antibody-drug conjugate, 7 bispecific, 5 CAR T) and 153 patients with no prior BCMA-TT were infused with ide-cel, with a median follow-up duration of 4.5 and 6.0 months, respectively. Safety outcomes between cohorts were comparable. The prior BCMA-TT cohort had a lower overall response rate (74% versus 88%; p = 0.021), median duration of response (7.4 versus 9.6 months; p = 0.03), and median progression-free survival (3.2 months versus 9.0 months; p = 0.0002) compared to the cohort without prior BCMA-TT. All five patients who received a prior anti-BCMA CAR T responded to ide-cel, and survival outcomes were best for this subgroup. In conclusion, treatment with ide-cel yielded meaningful clinical responses in real-world patients exposed to a prior BCMA-TT, though response rates and durability were suboptimal compared to those not treated with a prior BCMA-TT.

We evaluated patients with relapsed multiple myeloma with renal impairment (RI) treated with standard of care idecabtagene vicleucel (ide-cel), as outcomes with chimeric antigen receptor (CAR) T-cell therapy are unknown in this population. RI was defined as creatinine clearance (CrCl)

Abstract The traditionally held assumption that photo-dependent processes are the predominant source of H2O2 in natural waters has been recently questioned by an increrasing body of evidence showing the ubiquitiousness of H2O2 in dark water bodies and in groundwater. In this study, we conducted field measurement of H2O2 in an intra-meander hyporheic zone and in surface water at East River, CO. On-site detection using a sensitive chemiluminescence method suggests H2O2 concentrations in groundwater ranging from 6 nM (at the most reduced region) to ~ 80 nM (in a locally oxygen-rich area) along the intra-meander transect with a maxima of 186 nM detected in the surface water in an early afternoon, lagging the maximum solar irradiance by ∼ 1.5 h. Our results suggest that the dark profile of H2O2 in the hyporheic zone is closely correlated to local redox gradients, indicating that interactions between various redox sensitive elements could play an essential role. Due to its transient nature, the widespread presence of H2O2 in the hyporheic zone indicates the existence of a sustained balance between H2O2 production and consumption, which potentially involves a relatively rapid succession of various biogeochemically important processes (such as organic matter turnover, metal cycling and contaminant mobilization). More importantly, this study confirmed the occurrence of reactive oxygen species at a subsurface redox transition zone and further support our understanding of redox boundaries on reactive oxygen species generation and as key locations of biogeochemical activity.

Music history is often pushed to the margins of the public school curriculum. Faced with limited time and resources, teachers need to find concise, non-traditional ways to reintegrate history with performance and the other liberal arts. At the same time, they need to demonstrate, not just describe, the many ways in which music is intertwined with history and culture.

This article urges musicologists to consider ways in which to connect with pre-collegiate education. Ideas presented include connecting with local schools and national teacher organizations, creating courses and workshops, and looking for ways our research might be presented to a broader audience. Extending our outreach promotes the health of our discipline and strengthens our presence in the face of financial setbacks and imposed curricular revisions.

A challenge that exists in higher education is the lack of relatability between students and teachers. This disconnect likely prevents students from asking for help before, during, and/or after class. One way to increase relatability between students and teachers is by having a simple 5-minute conversation during an individual meeting, where I asked four questions and listened to the answers. The purpose of these meetings was to foster a relationship between myself and my students, in the hopes that students would feel more comfortable asking for help during and outside of class. Students were offered a small amount of extra credit to meet with their human physiology professor during the first three weeks of the semester. To earn extra credit, students had to (1) Sign up for a five-minute meeting using a link posted on Canvas, (2) Find the office of the professor, and (3) Answer four questions. Students did not know the questions before hand which were: (1) Where are you from? (2) What is your career goal? (3) What is something unique about yourself? (4) What was the highlight of your break? During the 2022-23 academic year, I had [approximately equal] 350 individual meetings with students where I asked these four questions. In a follow-up, anonymous survey, a common theme from students was these meetings were beneficial because they became more comfortable, and it made them more likely to ask questions in the future. These meetings appeared to be effective at increasing student engagement during and outside of class.