journal
https://read.qxmd.com/read/38784023/lncrna-irain-overcomes-imatinib-resistance-in-chronic-myeloid-leukemia-via-nf-%C3%AE%C2%BAb-cd44-pathway-inhibition
#1
JOURNAL ARTICLE
Xijia Wang, Yutong Hou, Yizhu Lyu, Jiayin Zhou, Xin Zhang, Mohammad Arian Hassani, Dan Huang, Zhijia Zhao, Dong Zhou, Fang Xie, Xuehong Zhang, Jinsong Yan
The development of tyrosine kinase inhibitors (TKIs) has revolutionarily increased the overall survival of patients with chronic myeloid leukemia (CML). However, drug resistance remains a major obstacle. Here, we demonstrated that a BCR-ABL1-independent long non-coding RNA, IRAIN , is constitutively expressed at low levels in CML, resulting in imatinib resistance. IRAIN knockdown decreased the sensitivity of CD34+ CML blasts and cell lines to imatinib, whereas IRAIN overexpression significantly increased sensitivity...
June 21, 2024: IScience
https://read.qxmd.com/read/38784022/mdm2-mdmx-inhibition-by-sulanemadlin-synergizes-with-anti-programmed-death-1-immunotherapy-in-wild-type-p53-tumors
#2
JOURNAL ARTICLE
Katrine Ingelshed, Marit M Melssen, Pavitra Kannan, Arun Chandramohan, Anthony W Partridge, Long Jiang, Fredrik Wermeling, David P Lane, Marika Nestor, Diana Spiegelberg
Immunotherapy has revolutionized cancer treatment but its efficacy depends on a robust immune response in the tumor. Silencing of the tumor suppressor p53 is common in tumors and can affect the recruitment and activation of different immune cells, leading to immune evasion and poor therapy response. We found that the p53 activating stapled peptide MDM2/MDMX inhibitor Sulanemadlin (ALRN-6924) inhibited p53 wild-type cancer cell growth in vitro and in vivo . In mice carrying p53 wild-type CT26.WT tumors, monotherapy with the PD-1 inhibitor DX400 or Sulanemadlin delayed tumor doubling time by 50% and 37%, respectively, while combination therapy decreased tumor doubling time by 93% leading to an increased median survival time...
June 21, 2024: IScience
https://read.qxmd.com/read/38784021/the-public-private-research-ecosystem-in-the-genome-editing-era
#3
JOURNAL ARTICLE
Rami M Major, Arlene M Davis, Gail E Henderson, Greg Inamine, John M Conley
Biomedical research in the US has long been conducted in a public-private (PP) "ecosystem." Today, especially with gene therapies and genome editing-based medicine, publicly funded researchers frequently hand off their research to the private sector for clinical development, often to small, venture capital-funded startups in which they have a financial interest. This trend raises ethical questions about conflicts of interest, effectiveness of regulatory oversight, and justice in therapy access, that we are addressing in a multi-year, multidisciplinary study of the evolving governance of genome editing...
June 21, 2024: IScience
https://read.qxmd.com/read/38784020/a-feasible-interlayer-strategy-for-simultaneous-light-and-heat-management-in-photothermal-catalysis
#4
JOURNAL ARTICLE
Yi Xiao, Kai Feng, Graham Dawson, Valeri P Tolstoy, Xingda An, Chaoran Li, Le He
Photothermal conversion represents one crucial approach for solar energy harvesting and its exploitation as a sustainable alternative to fossil fuels; however, an efficient, cost-effective, and generalized approach to enhance the photothermal conversion processes is still missing. Herein, we develop a feasible and efficient photothermal conversion strategy that achieves simultaneous light and heat management using supported metal clusters and WSe2 interlayer toward enhanced CO2 hydrogenation photothermal catalysis...
June 21, 2024: IScience
https://read.qxmd.com/read/38784019/automated-3d-cytoplasm-segmentation-in-soft-x-ray-tomography
#5
JOURNAL ARTICLE
Ayse Erozan, Philipp D Lösel, Vincent Heuveline, Venera Weinhardt
Cells' structure is key to understanding cellular function, diagnostics, and therapy development. Soft X-ray tomography (SXT) is a unique tool to image cellular structure without fixation or labeling at high spatial resolution and throughput. Fast acquisition times increase demand for accelerated image analysis, like segmentation. Currently, segmenting cellular structures is done manually and is a major bottleneck in the SXT data analysis. This paper introduces ACSeg, an automated 3D cytoplasm segmentation model...
June 21, 2024: IScience
https://read.qxmd.com/read/38784018/quantitative-proteomics-reveals-the-dynamic-proteome-landscape-of-zebrafish-embryos-during-the-maternal-to-zygotic-transition
#6
JOURNAL ARTICLE
Fei Fang, Daoyang Chen, Abdul Rehman Basharat, William Poulos, Qianyi Wang, Jose B Cibelli, Xiaowen Liu, Liangliang Sun
Maternal-to-zygotic transition (MZT) is central to early embryogenesis. However, its underlying molecular mechanisms are still not well described. Here, we revealed the expression dynamics of 5,000 proteins across four stages of zebrafish embryos during MZT, representing one of the most systematic surveys of proteome landscape of the zebrafish embryos during MZT. Nearly 700 proteins were differentially expressed and were divided into six clusters according to their expression patterns. The proteome expression profiles accurately reflect the main events that happen during the MZT, i...
June 21, 2024: IScience
https://read.qxmd.com/read/38784017/ai-and-climate-resilience-governance
#7
REVIEW
Sara Mehryar, Vahid Yazdanpanah, Jeffrey Tong
While artificial intelligence (AI) offers promising solutions to address climate change impacts, it also raises many application limitations and challenges. A risk governance perspective is used to analyze the role of AI in supporting decision-making for climate adaptation, spanning risk assessment, policy analysis, and implementation. This comprehensive review combines expert insights and systematic literature review. The study's findings indicate a large emphasis on applying AI to climate "risk assessments," particularly regarding hazard and exposure assessment, but a lack of innovative approaches and tools to evaluate resilience and vulnerability as well as prioritization and implementation process, all of which involve subjective, qualitative, and context-specific elements...
June 21, 2024: IScience
https://read.qxmd.com/read/38784016/mitochondrial-clearance-and-increased-hsf-1-activity-are-coupled-to-promote-longevity-in-fasted-caenorhabditis-elegans
#8
JOURNAL ARTICLE
Nikolaos Tataridas-Pallas, Yahyah Aman, Rhianna Williams, Hannah Chapman, Kevin J H Cheng, Casandra Gomez-Paredes, Gillian P Bates, John Labbadia
Fasting has emerged as a potent means of preserving tissue function with age in multiple model organisms. However, our understanding of the relationship between food removal and long-term health is incomplete. Here, we demonstrate that in the nematode worm Caenorhabditis elegans, a single period of early-life fasting is sufficient to selectively enhance HSF-1 activity, maintain proteostasis capacity and promote longevity without compromising fecundity. These effects persist even when food is returned, and are dependent on the mitochondrial sirtuin, SIR-2...
June 21, 2024: IScience
https://read.qxmd.com/read/38784015/predicting-treatment-outcome-using-kinome-activity-profiling-in-her2-breast-cancer-biopsies
#9
JOURNAL ARTICLE
Donna O Debets, Erik L de Graaf, Marte C Liefaard, Gabe S Sonke, Esther H Lips, Anna Ressa, Maarten Altelaar
In this study, we measured the kinase activity profiles of 32 pre-treatment tumor biopsies of HER2-positive breast cancer patients. The aim of this study was to assess the prognostic potential of kinase activity levels, to identify potential mechanisms of resistance and to predict treatment success of HER2-targeted therapy combined with chemotherapy. Indeed, our system-wide kinase activity analysis allowed us to link kinase activity to treatment response. Overall, high kinase activity in the HER2-pathway was associated with good treatment outcome...
June 21, 2024: IScience
https://read.qxmd.com/read/38784014/erratum-a-bacterial-pathogen-senses-host-mannose-to-coordinate-virulence
#10
Lifan Wei, Haoxian Qiao, Brandon Sit, Kaiyu Yin, Guanhua Yang, Ruiqing Ma, Jiabao Ma, Chun Yang, Jun Yao, Yue Ma, Jingfan Xiao, Xiaohong Liu, Yuanxing Zhang, Matthew K Waldor, Qiyao Wang
[This corrects the article DOI: 10.1016/j.isci.2019.09.028.].
June 21, 2024: IScience
https://read.qxmd.com/read/38784013/dysregulated-innate-immune-signaling-cooperates-with-runx1-mutations-to-transform-an-mds-like-disease-to-aml
#11
JOURNAL ARTICLE
Laura Barreyro, Avery M Sampson, Kathleen Hueneman, Kwangmin Choi, Susanne Christie, Vighnesh Ramesh, Michael Wyder, Dehua Wang, Mario Pujato, Kenneth D Greis, Gang Huang, Daniel T Starczynowski
Dysregulated innate immune signaling is linked to preleukemic conditions and myeloid malignancies. However, it is unknown whether sustained innate immune signaling contributes to malignant transformation. Here we show that cell-intrinsic innate immune signaling driven by miR-146a deletion (miR-146aKO ), a commonly deleted gene in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), cooperates with mutant RUNX1 (RUNX1mut ) to initially induce marrow failure and features of MDS. However, miR-146aKO hematopoietic stem and/or progenitor cells (HSPCs) expressing RUNX1mut eventually progress to a fatal AML...
June 21, 2024: IScience
https://read.qxmd.com/read/38784012/limitations-of-fluorescent-timer-protein-maturation-kinetics-to-isolate-transcriptionally-synchronized-human-neural-progenitor-cells
#12
JOURNAL ARTICLE
Manuel Peter, Seth Shipman, Jaewon Heo, Jeffrey D Macklis
Differentiation of human pluripotent stem cells (hPSCs) into subtype-specific neurons holds substantial potential for disease modeling in vitro . For successful differentiation, a detailed understanding of the transcriptional networks regulating cell fate decisions is critical. The heterochronic nature of neurodevelopment, during which distinct cells in the brain and during in vitro differentiation acquire their fates in an unsynchronized manner, hinders pooled transcriptional comparisons. One approach is to "translate" chronologic time into linear developmental and maturational time...
June 21, 2024: IScience
https://read.qxmd.com/read/38784011/the-global-contribution-of-vultures-towards-ecosystem-services-and-sustainability-an-experts-perspective
#13
JOURNAL ARTICLE
Andrea Santangeli, Sergio A Lambertucci, Antoni Margalida, Tomaso Carucci, Andre Botha, Katherine Whitehouse-Tedd, Tommaso Cancellario
The ecosystem services framework is essential for biodiversity conservation, emphasizing the role of nature in achieving sustainable development goals (SDGs). This study offers a global view on vulture-associated ecosystem services and their SDG contributions, based on insights from 206 experts. The findings reveal global consensus on the importance of vultures in regulation and maintenance services, such as waste recycling and disease control. Cultural services attributed to vultures are moderate and vary regionally...
June 21, 2024: IScience
https://read.qxmd.com/read/38784010/distinct-rich-and-diverse-clubs-regulate-coarse-and-fine-binocular-disparity-processing-evidence-from-stereoscopic-task-based-fmri
#14
JOURNAL ARTICLE
Kritika Lohia, Rijul Saurabh Soans, Rohit Saxena, Kabir Mahajan, Tapan K Gandhi
While cortical regions involved in processing binocular disparities have been studied extensively, little is known on how the human visual system adapts to changing disparity magnitudes. In this paper, we investigate causal mechanisms of coarse and fine binocular disparity processing using fMRI with a clinically validated, custom anaglyph-based stimulus. We make use of Granger causality and graph measures to reveal the existence of distinct rich and diverse clubs across different disparity magnitudes. We demonstrate that Middle Temporal area (MT) plays a specialized role with overlapping rich and diverse characteristics...
June 21, 2024: IScience
https://read.qxmd.com/read/38784009/yap-condensates-are-highly-organized-hubs
#15
JOURNAL ARTICLE
Siyuan Hao, Ye Jin Lee, Nadav Benhamou Goldfajn, Eduardo Flores, Jindayi Liang, Hannah Fuehrer, Justin Demmerle, Jennifer Lippincott-Schwartz, Zhe Liu, Shahar Sukenik, Danfeng Cai
YAP/TEAD signaling is essential for organismal development, cell proliferation, and cancer progression. As a transcriptional coactivator, how YAP activates its downstream target genes is incompletely understood. YAP forms biomolecular condensates in response to hyperosmotic stress, concentrating transcription-related factors to activate downstream target genes. However, whether YAP forms condensates under other signals, how YAP condensates organize and function, and how YAP condensates activate transcription in general are unknown...
June 21, 2024: IScience
https://read.qxmd.com/read/38784008/tudca-alleviates-atherosclerosis-by-inhibiting-aim2-inflammasome-and-enhancing-cholesterol-efflux-capacity-in-macrophage
#16
JOURNAL ARTICLE
Xuyang Wang, Yuesheng Zhang, Luping Du, Zhengchen Jiang, Yan Guo, Kai Wang, Yijiang Zhou, Xiang Yin, Xiaogang Guo
Cholesterol efflux capacity (CEC) dysfunction in macrophages is important in atherosclerosis. However, the mechanism underlying CEC dysfunction remains unclear. We described the characteristics of ATF4 and inflammasome activation in macrophages during atherosclerosis through scRNA sequencing analysis. Then model of hyperlipemia was established in ApoE-/- mice; some were treated with tauroursodeoxycholic acid (TUDCA). TUDCA decreased the ATF4, Hspa, and inflammasome activation, reduced plaque area of the artery, and promoted CEC in macrophages...
June 21, 2024: IScience
https://read.qxmd.com/read/38784007/vdac1-interacting-molecules-promote-cell-death-in-cancer-organoids-through-mitochondrial-dependent-metabolic-interference
#17
JOURNAL ARTICLE
Stefano Conti Nibali, Silvia De Siervi, Enrico Luchinat, Andrea Magrì, Angela Messina, Lorenza Brocca, Stefania Mantovani, Barbara Oliviero, Mario U Mondelli, Vito De Pinto, Cristian Turato, Cristina Arrigoni, Marco Lolicato
The voltage-dependent anion-selective channel isoform 1 (VDAC1) is a pivotal component in cellular metabolism and apoptosis with a prominent role in many cancer types, offering a unique therapeutic intervention point. Through an in-silico -to- in-vitro approach we identified a set of VA molecules (VDAC Antagonists) that selectively bind to VDAC1 and display specificity toward cancer cells. Biochemical characterization showed that VA molecules can directly interact with VDAC1 with micromolar affinity by competing with the endogenous ligand NADH for a partially shared binding site...
June 21, 2024: IScience
https://read.qxmd.com/read/38784006/rsu-1-regulates-the-integrity-of-dense-bodies-in-muscle-cells-of-aging-caenorhabditis-elegans
#18
JOURNAL ARTICLE
Ling Jiang, Xinyan Wang, Dandan Zhang, Karen Wing Yee Yuen, Yu Chung Tse
Muscle contraction is vital for animal survival, and the sarcomere is the fundamental unit for this process. However, the functions of many conserved sarcomere proteins remain unknown, as their mutants do not exhibit obvious defects. To address this, Caenorhabditis elegans was utilized as a model organism to investigate RSU-1 function in the body wall muscle. RSU-1 is found to colocalize with UNC-97 at the dense body and M-line, and it is particularly crucial for regulating locomotion in aging worms, rather than in young worms...
June 21, 2024: IScience
https://read.qxmd.com/read/38784005/the-relativity-of-reaching-motion-of-the-touched-surface-alters-the-trajectory-of-hand-movements
#19
JOURNAL ARTICLE
Colleen P Ryan, Simone Ciotti, Priscilla Balestrucci, Antonio Bicchi, Francesco Lacquaniti, Matteo Bianchi, Alessandro Moscatelli
For dexterous control of the hand, humans integrate sensory information and prior knowledge regarding their bodies and the world. We studied the role of touch in hand motor control by challenging a fundamental prior assumption-that self-motion of inanimate objects is unlikely upon contact. In a reaching task, participants slid their fingertips across a robotic interface, with their hand hidden from sight. Unbeknownst to the participants, the robotic interface remained static, followed hand movement, or moved in opposition to it...
June 21, 2024: IScience
https://read.qxmd.com/read/38784004/catalytic-conversion-of-chitin-based-biomass-to-nitrogen-containing-chemicals
#20
REVIEW
Xinlei Ji, Yufeng Zhao, Matthew Y Lui, László T Mika, Xi Chen
The exploration of renewable alternatives to fossil fuels for chemical production is indispensable to achieve the ultimate goals of sustainable development. Chitin biomass is an abundant platform feedstock that naturally bears both nitrogen and carbon atoms to produce nitrogen-containing chemicals (including organonitrogen ones and inorganic ammonia). The expansion of biobased chemicals toward nitrogen-containing ones can elevate the economic competitiveness and benefit the biorefinery scheme. This review aims to provide an up-to-date summary on the overall advances of the chitin biorefinery for nitrogen-containing chemical production, with an emphasis on the design of the catalytic systems...
June 21, 2024: IScience
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