Mary E.

In 2024, the global average temperature reached 1.55 °C above the pre-industrial level for the first time. However, we could still keep the long-term global average temperature below 2 °C if all possible measures are taken to mitigate greenhouse gases. It is widely accepted that methane (CH4) mitigation can slow global warming in the near term. Among all approaches toward this goal, the utilization of aerobic methanotrophs, which are natural catalysts for the conversion of CH4, emerges as a promising solution. Previously, we identified a candidate for CH4 mitigation, Methylotuvimicrobium buryatense 5GB1C, which exhibits a greater growth rate and CH4 consumption rate than other known methanotrophs at 500 ppm CH4. In this study, we address aspects of the practical applications of this methanotroph for CH4 mitigation. We first examined temperature and medium conditions to optimize M. buryatense 5GB1C growth at 500 ppm CH4. The results show that M. buryatense 5GB1C has a broad optimal temperature range for growth at 500 ppm, from 15 °C to 30 °C, and that its growth rate is consistently improved by 20–30% in 10-fold-diluted medium. Next, to demonstrate the feasibility of CH4 removal at low concentrations by this methanotroph, we applied it in a laboratory-scale packed-bed column reactor for the treatment of 500 ppm CH4 and tested different packing materials. The column reactor experiments revealed a maximum elimination capacity of 2.1 g CH4 m−3 h−1 with 2 mm cellulose beads as the packing material. These results demonstrate that with further technological innovation, this methanotroph has the potential for real-world methane mitigation.

Methane, a greenhouse gas which has a global warming potential 80 times greater than carbon dioxide on a 20-year time scale, greatly contributes to global warming. Removing 1 Gt of atmospheric methane by 2050 would limit global temperature increase from reaching 1.5 °C. Currently, biotrickling filter systems for removing atmospheric methane via methanotrophs exist, but not for very low methane concentrations (<1 v%). Recent work at the University of Washington to isolate and improve a microbial strain which thrives at 500 ppmv CH4 has removed one obstacle in making this technology feasible. In this study, techno-economic and environmental life cycle assessment analyses conducted on this process have assessed its economic feasibility, greenhouse gas reduction potential, and possible areas of improvement. Study results show that at 500 ppmv CH4, this process could remove atmospheric methane at a cost of USD 3992–5224/tCH4. The best-performing case also produces annual net reductions in warming potential by 276–311 tCO2e/120 m3 process unit deployed. Many opportunities exist to improve the outcomes of the baseline analysis even further, especially related to reducing the transport distance of media and harvested biomass.

A metagenomic screen identifies retron reverse transcriptases for precise genome-editing applications.

For five decades, Jim A. Estes studied sea otters in the Aleutian archipelago of Alaska, discovering how otters structured entire communities. By c...

Cutaneous squamous cell carcinoma (cSCC) is the second most prevalent skin cancer diagnosed worldwide after basal cell carcinoma. CSCC represents a growing global public health challenge due to its higher potential of local invasion, recurrence, and metastasis. Incidence rates of cSCC are projected to increase due to rising exposures to risks factors. Ultraviolet light exposure is the primary cause, and lighter skin pigmentation, immunosuppressive conditions and skin phototype are the primary risk factors. CSCC typically presents as a red, scaly, flat lesion (in situ tumors) or a red, firm, raised lesion with scale or erosion (invasive tumors). Surgical excision remains the standard-of-care for localized cSCC and is often curative. Although, most patients achieve favorable outcomes, a subset of cSCC exhibits a highly aggressive and metastatic phenotype (postoperative recurrence rates are approximately 5%). Addressing the clinical challenge posed by these high-risk cases requires a more comprehensive understanding of the underlying molecular drivers. This review examines the interaction between transglutaminase 2 (TG2) and the G-protein-coupled receptor 56 (GPR56) as a pivotal driver of the aggressive cSCC phenotype. This molecular axis is particularly significant for its role in the maintenance of epidermal cancer stem (ECS) cells, which contribute to tumor progression and therapy resistance. While the definitive link between the TG2-GPR56 complex and systemic metastasis in cSCC is currently being elucidated, significant evidence from analogous malignancies and in vitro keratinocyte models provides a clear mechanistic roadmap for its involvement in tumor invasion.

The anticancer ruthenium complex indazolium trans-[tetrachlorobis(1H-indazole) ruthenate (III)—also known as KP1019—inhibits cancer cell proliferation in vitro, causes tumor regression in animal models, and showed no dose-limiting toxicity in a phase I clinical trial. Previous studies found that KP1019 damages DNA in both cancer cells and the budding yeast Saccharomyces cerevisiae. To identify other potential targets of KP1019 along with pathways that modulate the drug’s cellular effects, we screened the yeast gene deletion strain library by quantitative high-throughput cell array phenotyping (Q-HTCP). Fitness differences, as judged by growth curve analysis, identified genes for which loss of function (gene deletion) interacts with (enhances or suppresses) KP1019 effects. Drug-enhancing deletions were enriched for DNA repair functions, consistent with DNA damage being a primary target of KP1019 in yeast. pH homeostasis also modified the effects of KP1019. Drug-suppressing deletions prominently involved ribosomal proteins. A mechanistic link between ribosomal protein function and KP1019 toxicity was supported by dose-dependent accumulation of Rpl7a-GFP in the nucleolus, which is a hallmark of ribosomal biogenesis stress. Furthermore, KP1019 acted synergistically with the TOR pathway inhibitor everolimus to inhibit cell proliferation. The resulting model, wherein KP1019 perturbs ribosome assembly, can inform the design of future combination therapies.

Background: Effectively managing acute postoperative pain after laparoscopic surgery (M-PALS) is essential to optimize outcomes, enhance recovery, and mitigate opioid-related risks. We aimed to systematically map evidence on effectiveness and harms of pharmacologic and non-pharmacologic interventions for M-PALS. Methods: We searched three databases (2012–2025) for randomized clinical trials (RCTs) that reported postoperative opioid use and pain-related outcomes. We assessed study quality using the Cochrane Risk of Bias (ROB)-2 tool. Results: From 7638 citations, we included 101 RCTs. Postoperative opioid use was reported variably (e.g., total use over 24 or 48 h postoperatively, frequency of rescue-opioid use, and time to first rescue-opioid use). One out of 101 RCTs evaluated opioid prescription at discharge. No RCT reported opioid use at ≥3 months postoperatively. Eleven strategies were evaluated in ≥2 RCTs, with usual care/ sham as comparators. None of the 101 RCTs favored usual care over any intervention for pain or opioid use outcomes. For regional anesthesia (21 RCTs total; 12 with low ROB), intraperitoneal/preperitoneal local anesthetic instillation (10 RCTs; 4 with low ROB), intravenous dexamethasone (3 RCTs; 1 with low ROB), and the Enhanced Recovery After Surgery (ERAS) protocol (3 RCTs; 0 with low ROB), compared to usual care, >50% of RCTs favored the intervention for reducing pain and opioid use. For adverse events, only 3 out of 101 RCTs favored comparators. Inconsistent outcome reporting across all RCTs and, for multimodal strategies, the uniqueness of intervention–comparator combinations hindered comparisons. Conclusions: Interventions for M-PALS appear safe, with no RCT indicating worse efficacy of intervention than usual care; but evidence regarding superiority is conflicting. Future research should establish standardized and longer-term core outcome sets and make head-to-head comparisons between optimal strategies.

Bronchopulmonary dysplasia (BPD) is the most common respiratory disease in preterm infants born at less than 28 weeks gestation. Most existing clinical prediction models for BPD show limited accuracy in predicting BPD development when validated using external data, stressing the need for novel biomarkers to identify at-risk infants for early and effective interventions. We leveraged existing frozen umbilical cord blood samples from the Northwestern University Cord Blood Biobank (NUCord) to perform parallel transcriptional and DNA methylation profiling in a pilot study. Chorioamnionitis-associated differentially expressed genes (DEGs) in our cohort included markers previously established in clinical and animal BPD studies, such as genes related to NF-κB signaling and immune responses. Importantly, these genes were highly associated with chorioamnionitis infection status specifically in preterm infants. We also identified that BPD development is associated with disrupted methylation signatures in microRNA genes and genes associated with glucose metabolism. Taken together, these exploratory findings suggest that BPD development and chorioamnionitis are associated with distinct transcriptomic and epigenetic signatures when compared with healthy term and preterm infants. These signatures may represent biomarkers measurable at birth that predict BPD development during a time window when preventative or therapeutic interventions could be applied.

Several thermogenic pathways have been described in adipose tissue, including calcium-mediated thermogenesis in beige adipocytes. We have previously shown that adipocyte-specific deletion of the RNA binding protein human antigen R (HuR; Elavl1) results in thermogenic dysfunction. RNA sequencing revealed the downregulation of several calcium transport genes upon HuR deletion. The goal of this work was to define the HuR-dependent mechanisms of calcium driven thermogenesis in brown adipocytes. Brown adipose tissue (BAT)-specific HuR-deletion (BAT-HuR−/−) mice have no changes in their body weight, glucose tolerance, adipose tissue weights, or lipid droplet size compared to control, but are cold intolerant following acute thermal challenge at 4 °C. We also found decreased expression of ryanodine receptor 2 (Ryr2) in BAT from BAT-HuR−/− mice. We show that genetic deletion or pharmacological inhibition of HuR blunts both the increase in cytosolic calcium and the β-adrenergic-mediated heat generation in stromal vascular fraction (SVF)-derived primary brown adipocytes. Mechanistically, we show that HuR directly binds and reduces the decay rate of Ryr2 mRNA in brown adipocytes, and stabilization of Ryr2 via S107 rescues the observed changes. In conclusion, our results suggest that HuR-dependent control of Ryr2 expression plays a significant role in the thermogenic function of brown adipose tissue through modulation of sarcoendoplasmic-reticulum calcium cycling.