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Intracellular phase separation is emerging as a universal principle for organizing biochemical reactions in time and space. It remains incompletely resolved how biological function is encoded in these assemblies and whether this depends on their material state. The conserved intrinsically disordered protein PopZ forms condensates at the poles of the bacterium Caulobacter crescentus , which in turn orchestrate cell-cycle regulating signaling cascades. Here we show that the material properties of these condensates are determined by a balance between attractive and repulsive forces mediated by a helical oligomerization domain and an expanded disordered region, respectively. A series of PopZ mutants disrupting this balance results in condensates that span the material properties spectrum, from liquid to solid. A narrow range of condensate material properties supports proper cell division, linking emergent properties to organismal fitness. We use these insights to repurpose PopZ as a modular platform for generating tunable synthetic condensates in human cells. “Intracellular phase separation is emerging as a universal principle for organizing biochemical reactions in time and space. Here the authors show that PopZ condensate dynamics support cell division and using PopZ modular architecture, the tunable PopTag platform was developed to enable designer condensates.”

Phospholipids are the most abundant component in lipid membranes and are essential for the structural and functional integrity of the cell. In eukaryotic cells, phospholipids are primarily synthesized de novo through the Kennedy pathway that involves multiple enzymatic processes. The terminal reaction is mediated by a group of cytidine-5′-diphosphate (CDP)-choline /CDP-ethanolamine-phosphotransferases (CPT/EPT) that use 1,2-diacylglycerol (DAG) and CDP-choline or CDP-ethanolamine to produce phosphatidylcholine (PC) or phosphatidylethanolamine (PE) that are the main phospholipids in eukaryotic cells. Here we present the structure of the yeast CPT1 in multiple substrate-bound states. Structural and functional analysis of these binding-sites reveal the critical residues for the DAG acyl-chain preference and the choline/ethanolamine selectivity. Additionally, we present the structure in complex with a potent inhibitor characterized in this study. The ensemble of structures allows us to propose the reaction mechanism for phospholipid biosynthesis by the family of CDP-alcohol phosphotransferases (CDP-APs). Here, the authors present the cryo-EM structure of yeast CPT1, a critical enzyme in phospholipid synthesis, identifying residues crucial for substrate preference. This enable a reaction mechanism for the family of CDP-alcohol phosphotransferases to be proposed.

Many cyanobacteria, which use light as an energy source via photosynthesis, have evolved the ability to guide their movement toward or away from a light source. This process, termed “phototaxis,” enables organisms to localize in optimal light environments for improved growth and fitness. Mechanisms of phototaxis have been studied in the coccoid cyanobacterium Synechocystis sp. strain PCC 6803, but the rod-shaped Synechococcus elongatus PCC 7942, studied for circadian rhythms and metabolic engineering, has no phototactic motility. In this study we report a recent environmental isolate of S. elongatus, the strain UTEX 3055, whose genome is 98.5% identical to that of PCC 7942 but which is motile and phototactic. A six-gene operon encoding chemotaxis-like proteins was confirmed to be involved in phototaxis. Environmental light signals are perceived by a cyanobacteriochrome, PixJSe (Synpcc7942_0858), which carries five GAF domains that are responsive to blue/green light and resemble those of PixJ from Synechocystis. Plate-based phototaxis assays indicate that UTEX 3055 uses PixJSe to sense blue and green light. Mutation of conserved functional cysteine residues in different GAF domains indicates that PixJSe controls both positive and negative phototaxis, in contrast to the multiple proteins that are employed for implementing bidirectional phototaxis in Synechocystis.

Circadian clocks are nearly ubiquitous throughout life, appearing in eukaryotes and prokaryotes alike. They are an adaptation that evolved to modify metabolism and behavior in anticipation of the daily fluctuation in light and other environmental conditions. One of the simplest organisms to posses a circadian clock is the photoautotrophic cyanobacterium Synechococcus elongatus PCC 7942. As an organism wholly dependent on the sun's energy, its biology is structured around the day-night cycle. Its metabolism, gene expression, and cellular organization are regulated in a circadian manner. Here, I investigate the potential role of circadian chromosome compaction in imparting rhythmicity to downstream gene expression. I used fluorescence microscopy to visualize chromosome compaction status and correlate it to rhythmic gene expression. I also investigated circadian changes in cellular organization using high-resolution cryo-electron tomography (CET) to visualize cells in a near-native state. I report interesting subcellular structures and features that have not been observed previously. In support of CET as a maturing tool for cell biology, I present data and considerations for sample preparation and downstream data analysis.

Many cyanobacteria, which use light as an energy source via photosynthesis, have evolved the ability to guide their movement toward or away from a light source. This process, termed “phototaxis,” enables organisms to localize in optimal light environments for improved growth and fitness. Mechanisms of phototaxis have been studied in the coccoid cyanobacteriumSynechocystissp. strain PCC 6803, but the rod-shapedSynechococcus elongatusPCC 7942, studied for circadian rhythms and metabolic engineering, has no phototactic motility. In this study we report a recent environmental isolate ofS. elongatus, the strain UTEX 3055, whose genome is 98.5% identical to that of PCC 7942 but which is motile and phototactic. A six-gene operon encoding chemotaxis-like proteins was confirmed to be involved in phototaxis. Environmental light signals are perceived by a cyanobacteriochrome, PixJSe(Synpcc7942_0858), which carries five GAF domains that are responsive to blue/green light and resemble those of PixJ fromSynechocystis. Plate-based phototaxis assays indicate that UTEX 3055 uses PixJSeto sense blue and green light. Mutation of conserved functional cysteine residues in different GAF domains indicates that PixJSecontrols both positive and negative phototaxis, in contrast to the multiple proteins that are employed for implementing bidirectional phototaxis inSynechocystis.

Phospholipids are the most abundant component in lipid membranes and are essential for the structural and functional integrity of the cell. In eukaryotic cells, phospholipids are primarily synthesized de novo through the Kennedy pathway that involves multiple enzymatic processes. The terminal reaction is mediated by a group of cytidine-5’-diphosphate (CDP)-choline /CDP-ethanolamine-phosphotransferases (CPT/EPT) that use 1,2-diacylglycerol (DAG) and CDP-choline or CDP-ethanolamine to produce phosphatidylcholine (PC) or phosphatidylethanolamine (PE) those are the main phospholipids in eukaryotic cells. Here we present the structure of the yeast CPT1 in multiple substrate-bound states. Structural and functional analysis of these binding-sites reveal the critical residues for the DAG acyl-chain preference and the choline/ethanolamine selectivity. Additionally, we present the structure in complex with a potent inhibitor characterized in this study. The ensemble of structures allows us to propose the reaction mechanism for phospholipid biosynthesis by the family of CDP-alcohol phosphatidyltransferases (CDP-APs).

Abstract Phase separation is emerging as a universal principle for how cells use dynamic subcompartmentalization to organize biochemical reactions in time and space1,2. Yet, whether the emergent physical properties of these biomolecular condensates are important for their biological function remains unclear. The intrinsically disordered protein PopZ forms membraneless condensates at the poles of the bacterium Caulobacter crescentus and selectively sequesters kinase-signaling cascades to regulate asymmetric cell division3–5. By dissecting the molecular grammar underlying PopZ phase separation, we find that unlike many eukaryotic examples, where unstructured regions drive condensation6,7, a structured domain of PopZ drives condensation, while conserved repulsive features of the disordered region modulate material properties. By generating rationally designed PopZ mutants, we find that the exact material properties of PopZ condensates directly determine cellular fitness, providing direct evidence for the physiological importance of the emergent properties of biomolecular condensates. Our work codifies a clear set of design principles illuminating how sequence variation in a disordered domain alters the function of a widely conserved bacterial condensate. We used these insights to repurpose PopZ as a modular platform for generating synthetic condensates of tunable function in human cells. Competing Interest Statement A.S.H. is a scientific consultant with Dewpoint Therapeutics. A.D.G. has served as a consultant for Aquinnah Pharmaceuticals, Prevail Therapeutics and Third Rock Ventures and is a scientific founder of Maze Therapeutics. L.S. is on the board of Pacific Biosciences. K.L., S.B, A.D.G, and L.S. have submitted a patent application relating to pieces of this work (PCT/US2020/063245). Footnotes * ↵# emails: agitler{at}stanford.edu, shapiro{at}stanford.edu

Adverse events also had double counting, with a revised meta-analysis showing an increased 5% (3–7%; 0%) rate of grade 3–4 adverse events, or 5·9% (23/393) in raw proportions. [...]the use of single-arm meta-analyses for comparison is primarily flawed. [...]Huang and colleagues’ suggestion that SBRT could be advantageous for treating larger RCCs is premature due to methodological flaws. Supplementary Material Supplementary appendix Reference in study by Huang et al (2025) 1 Example of centre included in IPDMA * Recruitment/inclusion period Funayama et al (2019) 33 University of Yamanashi (Kofu, Japan) August 2007–June 2016 Grub et al (2021) † 37 University Hospitals Seidman Cancer Center (Cleveland, OH, USA) Since May 2011 Ponsky et al (2015) 27 University Hospitals Seidman Cancer Center (Cleveland, OH, USA) June 2006–August 2011 Hannan et al (2023) 18 University of Texas Southwestern Medical Center (Dallas, TX, USA) September 2014–October 2019 Glicksman et al (2023) ‡ 17 Juravinski Cancer Centre (Hamilton, ON, Canada) 2012–20 Chang et al (2016) 28 Sunnybrook Health Sciences Centre (Toronto, ON, Canada) Jan 1, 2012–April 1, 2015 Sun et al (2016) 29 Beth Israel Deaconess Medical Center (Boston, MA, USA) May 2006–May 2011 Siva et al (2017) 31 Peter MacCallum Cancer Centre (Melbourne, VIC, Australia) 2012–14 Table Studies included in meta-analysis that are potentially double counted from IPDMA

Percutaneous image-guided ablation (IGA) has emerged as an established alternative to surgical management for small renal masses. This comprehensive review examines traditional and emerging indications, energy sources, techniques, and future developments in IGA for renal cancer treatment. Traditionally, IGA has been indicated for frail or comorbid patients, those with solitary kidneys or chronic kidney disease, and those with histologically proven renal cell carcinomas less than 4 cm in size. Recent evidence supports expanding these indications to include T1b or T2 tumours and hereditary or recurrent renal cell carcinomas. The use of IGA combined with pre-ablation transarterial embolisation is discussed herein. This review then explores traditional energy sources including radiofrequency ablation, cryoablation, and microwave ablation, highlighting their respective advantages and limitations. Emerging technologies such as irreversible electroporation and histotripsy, as promising alternatives, are then presented, highlighting their advantage of being able to treat tumours near critical structures. Future research priorities highlight the need to establish high-quality evidence through innovative trial designs, as well as taking patient-reported outcome measures into account. Health economic considerations are key to ensuring that ablation therapies are cost-effective. The integration of artificial intelligence and radiomics shows vast potential for improving patient selection and treatment outcomes. Additionally, the immunomodulatory effects of ablative therapies suggest possible synergistic benefits when combined with immunotherapy which also require exploration in future research. Technological advancement and research developments will continue to broaden the role of IGA in clinical practice.