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作者：Hosseini, Amir; Qiu, Xing; Xiong, Yan; Chiang, Ki Him Nicholas; Catlett, Jerrel; Kaltheuner, Ines; Deng, Zhijie; Ghosh, Sudipta; Shi, Yang; Jin, Jian
作者单位：Ludwig Institute for Cancer Research; University of Oxford; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai
摘要：Aberrant expression of lysine-specific demethylase 1 (LSD1) has been implicated in various cancers, including acute myeloid leukemia (AML). Recent studies have revealed both catalytic and noncatalytic oncogenic functions of LSD1, which cannot be effectively addressed by traditional small-molecule inhibitors. Therefore, to remove LSD1 and mitigate its oncogenic activity, we utilized the proteolysis-targeting chimera (PROTAC) approach and developed an LSD1 PROTAC degrader MS9117, which recruits ...
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作者：Zhu, Yicheng; Xue, Boyi; Sun, Yuncong; Geng, Qi; Chen, Yuping; Chen, Xianfeng; Jiang, Xiaoshun; Ge, Li; Wan, Wenjie
作者单位：Shanghai Jiao Tong University; Shanghai Jiao Tong University; Nanjing University; Nanjing University; City University of New York (CUNY) System; College of Staten Island (CUNY)
摘要：The ability to coherently manipulate phonons through light permits cooling and heating microscale quantum systems for various critical fields in metrology, information processing, and sensing. However, these physical systems often are hard to isolate and open for exchanging energy externally, making themselves non-Hermitian. Here, we experimentally observe a super-cooling/heating state in a non-Hermitian phononic dimer, where the two independent phonon modes of distinct cooling/heating rates b...
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作者：Austin, Cary D.; Lawrence, David A.; Peden, Andrew A.; Varfolomeev, Eugene E.; Totpal, Klara; De Maziere, Ann M.; Klumperman, Judith; Arnott, David; Pham, Victoria; Scheller, Richard H.; Ashkenazi, Avi
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作者：Li, Dongyu; Chen, Hongwen; Vale, Goncalo; Meinhardt, Nadia Elghobashi -; Hatton, Alexandra; Rong, Shunxing; McDonald, Jeffrey G.; Li, Xiaochun
作者单位：University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; University College Dublin; University of Texas System; University of Texas Southwestern Medical Center
摘要：Homologous proteins share similar sequences, enabling them to work together in cells to support normal physiological functions. Phosphatidylserine synthases 1 and 2 (PSS1 and PSS2) are homologous enzymes that catalyze the synthesis of phosphatidylserine (PS) from different substrates. PSS2 shows a preference for phosphatidylethanolamine (PE) as its substrate, whereas PSS1 can utilize either PE or phosphatidylcholine. Previous their homology, our findings reveal that PSS2 exerts an opposing eff...
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作者：Prota, Gennaro; Berloffa, Giuliano; Awad, Wael; Vacchini, Alessandro; Chancellor, Andrew; Schaefer, Verena; Constantin, Daniel; Littler, Dene R.; Colombo, Rodrigo; Nosi, Vladimir; Mori, Lucia; Rossjohn, Jamie; De Libero, Gennaro
作者单位：University of Basel; Monash University; Monash University; Cardiff University
摘要：Mitochondria coordinate several metabolic pathways, producing metabolites that influence the immune response in various ways. It remains unclear whether mitochondria impact antigen presentation by the MHC-class-I-related antigen-presenting molecule, MR1, which presents small molecules to MR1-restricted T-lymphocytes. Here, we demonstrate that mitochondrial complex III and the enzyme dihydroorotate dehydrogenase are essential for the cell-surface expression of MR1 and for generating uridine-and...
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作者：Fritts, Ryan K.; Ebmeier, Christopher C.; Copley, Shelley D.
作者单位：University of Colorado System; University of Colorado Boulder; University of Colorado System; University of Colorado Boulder; University of Colorado System; University of Colorado Boulder
摘要：Gene amplification can drive adaptation by rapidly increasing the cellular dosage of critical gene products. Segmental amplifications often encompass large genomic regions surrounding the gene(s) under selection for higher dosage. Overexpression of coamplified neighboring genes imposes a substantial metabolic burden. While compensatory mutations can decrease inappropriate overexpression of coamplified genes, it takes time for such mutations to arise. The extent to which intrinsic regulatory me...
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作者：Yang, Qing; Chen, Di; Liu, Xi; Li, Wenjie; Zheng, Huizhen; Cai, Xiaoming; Li, Ruibin
作者单位：Soochow University - China; Soochow University - China; Soochow University - China; Technical University of Ostrava
摘要：Breast milk is crucial for infant health, offering essential nutrients and immune protection. However, despite increasing exposure risks from nanoparticles (NPs), their potential infiltration into human breast milk remains poorly understood. This study provides a comprehensive chemical profile of NPs in human breast milk, analyzing their elemental composition, surface charge, hydrodynamic size, and crystallinity. NPs were detected in 42 out of 53 milk samples, with concentrations reaching up t...
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作者：Ku, Hui - Yu; Bilder, David
作者单位：University of California System; University of California Berkeley
摘要：While paradigms for patterning of cell fates in development are well established, paradigms for patterning morphogenesis, particularly when organ shape is influenced by the extracellular matrix (ECM), are not. Morphogenesis of the Drosophila egg chamber (follicle) depends on anterior-posterior distribution of basement membrane (BM) components such as Collagen IV (Col4), whose gradient creates tissue mechanical properties that specify the degree of elongation. Here, we show that the gradient is...
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作者：Roy, Pritam Kumar; Takai, Yui; Matsubara, Rui; Tenjimbayashi, Mizuki; Mouterde, Timothee
作者单位：University of Tokyo; National Institute for Materials Science
摘要：In the insect realm, liquids become traps due to capillary and viscous forces dominant at their scale. Yet, aphids handle the highly viscous honeydew droplets they secrete by coating them with hydrophobic wax powder which maintains an air layer between their body and the liquid. These coated droplets, known as liquid marbles, exhibit low friction and high mobility, enabling manipulation of small liquid volumes which is useful for biomedical analysis where sample volumes are limited, chemistry ...
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作者：Woods, Christopher N.; Janowska, Maria K.; Ulmer, Lindsey D.; Sidhu, Jasleen Kaur; Stone, Natalie L.; James, Ellie I.; Guttman, Miklos; Bush, Matthew F.; Klevit, Rachel E.
作者单位：University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle
摘要：Found from bacteria to humans, small heat shock proteins (sHSPs) are the least understood protein chaperones. HSPB5 (or alpha B-crystallin) is among the most widely expressed of the 10 human sHSPs, including in muscle, brain, and eye lens where it is constitutively present at high levels. A high content of disorder in HSPB5 has stymied efforts to uncover how its structure gives rise to function. To uncover its mechanisms of action, we compared human HSPB5 and two disease-associated mutants, R1...
