Search

Scleractinian corals are increasingly subjected to local stressors combined with global changes. In subtropical areas, corals exhibit metabolic plasticity and resilience in response to variability and extremes in local temperature, salinity, and light; however, the physiological mechanisms by which corals acclimate or adapt to these changing conditions remain disputed. We assessed the physiological status of the coral Platygyra carnosa during a two-year in situ monitoring survey. To obtain metabolic rates (respiration and photosynthesis), photochemical efficiency (Fv / Fm), and biocalcification measurements, non-invasive techniques such as underwater respirometry, Pulse Amplitude Modulated (PAM) fluorometry, total alkalinity measurements, and digital photography were used. Our findings show clear seasonality in water quality parameters, which affected coral health. Elevated temperatures during the summer were below the maximum monthly mean < 31°C) but reduced the energetic productivity of corals (-44% relative to winter). Fluctuations in salinity (25–38 ppt) and pH (7.65–8.44) were linked to rainfall and reduced calcification rates. The conditions during the spring were favorable for coral metabolism and calcification (+20% relative to summer). Overall, our research demonstrates that the metabolic plasticity of P. carnosa in response to shifts in seawater quality allows this species to survive ongoing environmental change. Our in situ observations provide fundamental insights into coral response mechanisms under changing environmental conditions and contribute to projections of coral health under future scenarios of global change.

Influential theories of motivated reasoning, as well as real-world anecdotal examples, would suggest that voters do not always penalize legislators from their own party for alleged immoral behavior, such as sexual harassment. But very little empirical evidence exists on how voters react to sexual misconduct allegations, especially since the start of the #MeToo movement. We examine how partisanship and sexist attitudes shape individuals’ reactions to sexual harassment allegations about a politician. Using a pretest–posttest online experiment, we randomize both the party affiliation of the accused legislator as well as the severity of the allegations. Overall, we find some evidence of partisan bias, but that there may be a limit. Subjects were more forgiving of an accused co-partisan legislator than a legislator of the opposing party in their overall evaluation and their perceptions of punitive repercussions, but their levels of electoral support decreased just as much for co-partisans as they did for opposing partisans. Importantly, these reactions are strongly conditioned by sexism; as subjects’ levels of sexism increase, the otherwise large and negative effect of allegations on evaluations of favorability and electoral support disappears.

While poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) have improved the prognosis of ovarian high-grade serous carcinoma (HGSC) tumors that are homologous recombination (HR) deficient (HRD), new therapeutic strategies are needed for tumors that are HR proficient (HRP) because they demonstrate greater resistance to current treatments and thus have poorer clinical outcomes. Additionally, clinical precautionary statements regarding potential risks associated with PARPi, such as myelodysplastic syndrome, highlight the need for combinatorial approaches that can lessen the dose and duration of PARPi treatment to reduce toxicities. Here, we evaluated DNA double-strand damage repair pathways in HRD and HRP ovarian cancer cell lines and found that in HRD cell lines, PARPi therapy reduced non-homologous end joining (NHEJ)-mediated repair, specifically due to decreased theta-mediated end-joining. The combination of PARPi with ATM serine/threonine kinase inhibitor (ATMi) suppressed both NHEJ and HR pathways in HRD and HRP cell lines, with synergistic increases in apoptosis and decreases in cell viability and colony formation. Interestingly, PARPi plus ATMi also decreased NF-κB p65 phosphorylation, which was not observed when PARPi was combined with inhibition of the ATR kinase (ATRi). These findings indicate that PARPi plus ATMi is a promising strategy for HGSC independent of underlying tumor HR status.

Magnetic particle imaging (MPI) is an emerging noninvasive molecular imaging modality with high sensitivity and specificity, exceptional linear quantitative ability, and potential for successful applications in clinical settings. Computed tomography (CT) is typically combined with the MPI image to obtain more anatomical information. Herein, a deep learning‐based approach for MPI‐CT image segmentation is presented. The dataset utilized in training the proposed deep learning model is obtained from a transgenic mouse model of breast cancer following administration of indocyanine green (ICG)‐conjugated superparamagnetic iron oxide nanoworms (NWs‐ICG) as the tracer. The NWs‐ICG particles progressively accumulate in tumors due to the enhanced permeability and retention (EPR) effect. The proposed deep learning model exploits the advantages of the multihead attention mechanism and the U‐Net model to perform segmentation on the MPI‐CT images, showing superb results. In addition, the model is characterized with a different number of attention heads to explore the optimal number for our custom MPI‐CT dataset.

Type-I interferon (IFN-I) signaling is critical to maintaining antigen-presenting cell function for anti-tumor immunity. However, recent studies have suggested that IFN-I signaling may also contribute to more aggressive phenotypes, raising the possibility that IFN-I downstream signaling in cancer and myeloid cells may exert dichotomous functions.We analyzed the clinicopathologic correlation of cancer-specific IFN-I activation in 195 head and neck squamous cell carcinoma patients. We also characterized the immune impact of IFN-I receptor (IFNAR1)-deficiency in syngeneic tumor models using biochemistry, flow cytometry, and single-cell RNA-Seq. We stained HNSCC tissue microarrays with a sensitive IFN-I downstream signaling activation marker, MX1, and quantitated cancer cell-specific MX1 staining. Kaplan-Meier analysis revealed that MX1-high tumors exhibited worse survival, a phenotype that depends on the number of CD8+ intratumoral T-cells. We found that cancer-specific IFNAR1 engagement promotes cancer stemness and higher expression levels of suppressive immune checkpoint receptor ligands in cancer-derived exosomes. Notably, mice bearing Ifnar1-deficient tumors exhibited lower tumor burden, increased T-cell infiltration, reduced exhausted CD4+PD1high T-cells, and increased effector population CD8+IFN-γ+ T-cells. Then, we performed single-cell RNA-sequencing and discovered that cancer-specific IFN-I signaling not only restricts effector cells expansion but also dampens their functional fitness.The beneficial role of IFN-I activation is largely dependent on the myeloid compartment. Cancer-specific IFN-I receptor engagement promotes cancer stemness and the release of cancer-derived exosomes with high expression levels of immune checkpoint receptor ligands. Cancer-specific IFN-I activation is associated with poor immunogenicity and worse clinical outcomes in HNSCC.