Pair correlation microscopy of intracellular molecular transport
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Iron homeostasis and ferroptosis in muscle diseases and disorders: mechanisms and therapeutic prospects
The muscular system plays a critical role in the human body by governing skeletal movement, cardiovascular function, and the activities of digestive organs. Additionally, muscle tissues serve an endocrine function by secreting myogenic cytokines, thereby regulating metabolism throughout the entire body. Maintaining muscle function requires iron homeostasis. Recent studies suggest that disruptions in iron metabolism and ferroptosis, a form of iron-dependent cell death, are essential contributors to the progression of a wide range of muscle diseases and disorders, including sarcopenia, cardiomyopathy, and amyotrophic lateral sclerosis. Thus, a comprehensive overview of the mechanisms regulating iron metabolism and ferroptosis in these conditions is crucial for identifying potential therapeutic targets and developing new strategies for disease treatment and/or prevention. This review aims to summarize recent advances in understanding the molecular mechanisms underlying ferroptosis in the context of muscle injury, as well as associated muscle diseases and disorders. Moreover, we discuss potential targets within the ferroptosis pathway and possible strategies for managing muscle disorders. Finally, we shed new light on current limitations and future prospects for therapeutic interventions targeting ferroptosis.
Estrogen-related receptor alpha (ERRα) controls the stemness and cellular energetics of prostate cancer cells via its direct regulation of citrate metabolism and zinc transportation
Compared to most tumors that are more glycolytic, primary prostate cancer is less glycolytic but more dependent on TCA cycle coupled with OXPHOS for its energy demand. This unique metabolic energetic feature is attributed to activation of mitochondrial m-aconitase in TCA caused by decreased cellular Zn level. Evidence suggests that a small subpopulation of cancer cells within prostate tumors, designated as prostate cancer stem cells (PCSCs), play significant roles in advanced prostate cancer progression. However, their cellular energetics status is still poorly understood. Nuclear receptor ERRα (ESRRA) is a key regulator of energy metabolism. Previous studies characterize that ERRα exhibits an upregulation in prostate cancer and can perform multiple oncogenic functions. Here, we demonstrate a novel role of ERRα in the control of stemness and energetics metabolism in PCSCs via a mechanism of combined transrepression of Zn transporter ZIP1 in reducing intracellular Zn uptake and transactivation of ACO2 (m-aconitase) in completion of TCA cycle. Results also showed that restoration of Zn accumulation by treatment with a Zn ionophore Clioquinol could significantly suppress both in vitro growth of PCSCs and also their in vivo tumorigenicity, implicating that enhanced cellular Zn uptake could be a potential therapeutic approach for targeting PCSCs in advanced prostate cancer.
Epigenomics and transcriptomics association study of blood pressure and incident diagnosis of hypertension in twins
Hypertension is the most frequent health-related condition worldwide and is a primary risk factor for renal and cardiovascular diseases. However, the underlying molecular mechanisms are still poorly understood. To uncover these mechanisms, multi-omics studies have significant potential, but such studies are challenged by genetic and environmental confounding – an issue that can be effectively reduced by studying intra-pair differences in twins. Here, we coupled data on hypertension diagnoses from the nationwide Danish Patient Registry to a study population of 740 twins for whom genome-wide DNA methylation and gene expression data were available together with measurements of systolic and diastolic blood pressure. We investigated five phenotypes: incident hypertension cases, systolic blood pressure, diastolic blood pressure, hypertension (140/90 mmHg), and hypertension (130/80 mmHg). Statistical analyses were performed using Cox (incident cases) or linear (remaining) regression analyses at both the individual-level and twin pair-level. Significant genes (p < 0.05) at both levels and in both types of biological data were investigated by bioinformatic analyses, including gene set enrichment analysis and interaction network analysis. Overall, most of the identified pathways related to the immune system, particularly inflammation, and biology of vascular smooth muscle cell. Of specific genes, lysine methyltransferase 2 A (KMT2A) was found to be central for incident hypertension, ataxia-telangiectasia mutated (ATM) for systolic blood pressure, and beta-actin (ACTB) for diastolic blood pressure. Noteworthy, lysine methyltransferase 2A (KMT2A) was also identified in the systolic and diastolic blood pressure analyses. Here, we present novel biomarkers for hypertension. This study design is surprisingly rare in the field of hypertension.
Improving the thermoelectric performance of scandium nitride thin films by implanting helium ions
Ion implantation is a widely used technique to introduce defects in low-dimensional materials and tune their properties. Here, we investigate the thermoelectric properties of scandium nitride thin films implanted with helium ions, revealing a positive impact of defect engineering on thermoelectric performance. Transport properties modeling and electron microscopy provide insights on the defect distribution in the films. The electrical resistivity and Seebeck coefficient increase significantly in absolute values after implantation and partially recover upon annealing as some of the implantation-induced defects heal. The thermal conductivity decreases by 46 % post- implantation due to the formation of extended defects and nanocavities. Consequently, the thermoelectric figure of merit zT doubles for the sample annealed at 673 K. These findings highlight the potential of controlled ion implantation to enhance thermoelectric properties in thin films, paving the way for further optimization through defect engineering.
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