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Proteostasis failure:at the intersection between aging and Alzheimer's disease

Neural Regeneration Research 2025年第11期20卷 3221-3222页

作者： Natalia Poblete Claudio Hetz Center for Geroscience Brain Health and MetabolismSantiagoChile Biomedical Neuroscience Institute Faculty of MedicineUniversity of ChileSantiagoChile Program of Cellular and Molecular Biology Institute of Biomedical SciencesFaculty of MedicineUniversity of ChileSantiagoChile Buck Institute for Research on Aging NovatoCAUSA

Lifestyle and demographics of the world's population are causing serious health problems impacting the brain,increasing the incidence of Alzheimer's disease(AD)and other types of *** we have gained important insights into the pathogenic mechanisms of AD,only palliative care is available to *** is characterized by the abnormal deposition of protein aggregates in the brain formed by amyloid β and hyper-phosphorylated,Tau in addition to neuroinflammation.

关键词： Alzheimer amyloid stasis

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BEAGLE 2.0: A Web Server for RNA Secondary Structure Similarity Detection Leveraging SHAPE-directed RNA Structure Determination

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Journal of molecular biology 2025年

作者： Ballesio, F. Teofani, A. Carrino, C. Catalano, M. Nicolaeasa, M.L. Ausiello, G. Helmer-Citterich, M. Gherardini, P.F. Department of Biology University of Rome “Tor Vergata” Rome Italy Ph.D. Program in Cellular and Molecular Biology Department of Biology University of Rome ’Tor Vergata’ Rome Italy

Recent studies underscore the significant role of RNA secondary structures in various biological and pathological processes. Structural conservation can reveal homologies undetectable by sequence analysis alone, making accurate prediction and comparison of RNA secondary structures crucial. The BEAGLE algorithm enables pairwise alignments of RNA secondary structures through dynamic programming, leveraging the BEAR encoding for RNA secondary structures representation. Initially, BEAGLE was designed to perform pairwise alignments of user-provided RNAs or against a limited number of datasets. We now introduce BEAGLE 2.0, a web server designed to facilitate the search for structural similarities between user-provided RNA molecules and an expanded collection of RNA secondary structure datasets. These datasets include structures derived from SHAPE experiments in Homo sapiens, Mus musculus, Danio rerio, Escherichia coli, Bacillus subtilis, and various viruses, including SARS-CoV-2. It also incorporates predicted structures from the NONCODE database for a wide range of animals and plants, as well as a dataset of structures based on constraints derived from conserved positions within the families present in Rfam. Users can input RNA sequences or a combination of sequences and secondary structures in either dot-bracket or BEAR format. BEAGLE 2.0 outputs pairwise alignments with measures of structural similarity and statistical significance. Additionally, it offers a visual representation of the secondary structures, with structural elements highlighted in different colors. Overall, BEAGLE 2.0 enables searches in RNA structure datasets leveraging experimentally supported data, to identify structural similarities in RNAs of interest. BEAGLE 2.0 is available at https://***. © 2025

关键词： icSHAPE data integration non-coding RNAs (ncRNAs) RNA homology detection RNA secondary structure alignment RNA structural similarity search

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Machine learning and confirmatory factor analysis show that buprenorphine alters motor and anxiety-like behaviors in male, female, and obese C57BL/6J mice

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Journal of Neurophysiology 2025年第2期133卷 502-512页

作者： Sharma, Ohm Mykins, Michael Bergee, Rebecca E. Price, Joshua M. O’Neil, Michael A. Mickels, Nicole Von Hagen, Megan O’Connor, James Baghdoyan, Helen A. Lydic, Ralph Neuroscience Program in Psychology The University of Tennessee Knoxville TN United States Department of Biochemistry & Cellular and Molecular Biology The University of Tennessee Knoxville TN United States Office of Innovative Technologies The University of Tennessee Knoxville TN United States Department of Microbiology The University of Tennessee Knoxville TN United States Department of Biomedical Engineering The University of Tennessee Knoxville TN United States

Buprenorphine is an opioid approved for medication-assisted treatment of opioid use disorder. Used off-label, buprenorphine has been reported to contribute to the clinical management of anxiety. Although human anxiety is a highly prevalent disorder, anxiety is a latent construct that cannot be directly measured. The present study combined machine learning techniques and artificial intelligence with confirmatory factor analysis to evaluate the hypothesis that buprenorphine alters motor and anxiety-like behavior in C57BL/6J (B6) mice (n = 30) as a function of dose, sex, and body mass. After administration of saline (control) or buprenorphine, mice were placed on an elevated zero maze (EZM) for 5 min. Digital video of mouse behavior was uploaded to the cloud, and mouse position on the maze was tracked and analyzed with supervised machine learning and artificial intelligence. ANOVA and post hoc test showed that buprenorphine significantly altered five motor behaviors. Confirmatory factor analysis revealed that the latent construct of anxiety-like behavior accounted for a statistically significant amount of variance in all five motor behaviors. Copyright © 2025 the American Physiological Society.

关键词： animal emotions artificial intelligence convolutional neural network deep learning opioids

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New job for an old tool: PI3Kβ phosphorylates OGT to regulate acetyl-CoA in glioblastoma

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Trends in cell biology 2025年第5期35卷 361-363页

作者： Riley G Young Nusaiba N Ahmed Mauricio J Reginato Department of Biochemistry and Molecular Biology Drexel University College of Medicine Philadelphia PA USA. Department of Biochemistry and Molecular Biology Drexel University College of Medicine Philadelphia PA USA Translational and Cellular Oncology Program Sidney Kimmel Comprehensive Cancer Center Thomas Jefferson University Philadelphia PA USA. Electronic address: mjr53@drexel.edu.

Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta (PI3Kβ) is recognized for its role in cellular signaling as a lipid kinase. He and colleagues recently reported a non-canonical function of PI3Kβ where, under high glucose, it phosphorylates and activates O-GlcNAc transferase (OGT). This activation enhances ATP-citrate synthase (ACLY) O-GlcNAcylation, increasing acetyl-CoA production, fueling fatty acid metabolism and histone acetylation, and driving glioblastoma (GBM) growth.

关键词： ACLY HK1 O-GlcNAc transferase PI3Kβ acetyl-CoA acetylation glioblastoma kinase

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An innate drive to save a life

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Science (New York, N.Y.) 2025年第6736期387卷 827-828页

作者： William M Sheeran Zoe R Donaldson Department of Molecular Cellular and Developmental Biology University of Colorado Boulder Boulder CO USA. Medical Scientist Training Program University of Colorado School of Medicine Aurora CO USA. Department of Psychology and Neuroscience University of Colorado Boulder Boulder CO USA.

In mice, two brain regions drive the impulse to revive an unconscious companion.

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Invasion and metastasis in cancer:molecular insights and therapeutic targets

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Signal Transduction and Targeted Therapy 2025年第3期10卷 1503-1540页

作者： Yongxing Li Fengshuo Liu Qingjin Cai Lijun Deng Qin Ouyang Xiang H.-F.Zhang Ji Zheng Department of Urology Urologic Surgery CenterXinqiao HospitalThird Military Medical University(Army Medical University)ChongqingChina State Key Laboratory of Trauma and Chemical Poisoning Third Military Medical University(Army Medical University)ChongqingChina Lester and Sue Smith Breast Center Baylor College of MedicineHoustonTXUSA Dan L.Duncan Cancer Center Baylor College of MedicineHoustonTXUSA Department of Molecular and Cellular Biology Baylor College of MedicineHoustonTXUSA McNair Medical Institute Baylor College of MedicineHoustonTXUSA Graduate School of Biomedical Science Cancer and Cell Biology ProgramBaylor College of MedicineHoustonTXUSA Department of Medicinal Chemistry Third Military Medical University(Army Medical University)ChongqingChina

The progression of malignant tumors leads to the development of secondary tumors in various organs,including bones,the brain,liver,and *** metastatic process severely impacts the prognosis of patients,significantly affecting their quality of life and survival *** efforts have consistently focused on the intricate mechanisms underlying this process and the corresponding clinical management ***,a comprehensive understanding of the biological foundations of tumor metastasis,identification of pivotal signaling pathways,and systematic evaluation of existing and emerging therapeutic strategies are paramount to enhancing the overall diagnostic and treatment capabilities for metastatic ***,current research is primarily focused on metastasis within specific cancer types,leaving significant gaps in our understanding of the complex metastatic cascade,organ-specific tropism mechanisms,and the development of targeted *** this study,we examine the sequential processes of tumor metastasis,elucidate the underlying mechanisms driving organ-tropic metastasis,and systematically analyze therapeutic strategies for metastatic tumors,including those tailored to specific organ ***,we synthesize the most recent advances in emerging therapeutic technologies for tumor metastasis and analyze the challenges and opportunities encountered in clinical research pertaining to bone *** objective is to offer insights that can inform future research and clinical practice in this crucial field.

关键词： secondary tumors invasion metastatic process therapeutic targets molecular insights malignant tumors tumor metastasis metastasis

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Emerging Techniques in Spatial Multiomics: Fundamental Principles and Applications to Dermatology

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Journal of Investigative Dermatology 2025年第5期145卷 1017-1032页

作者： Jia, Bojing B. Sun, Bryan K. Lee, Ernest Y. Ren, Bing Bioinformatics and Systems Biology Graduate Program University of California San Diego La Jolla CA United States Medical Scientist Training Program University of California San Diego La Jolla CA United States Department of Dermatology University of California Irvine Irvine CA United States Department of Dermatology University of California San Francisco San Francisco CA United States Center for Epigenomics Department of Cellular & Molecular Medicine University of California San Diego La Jolla CA United States Institute of Genomic Medicine Moores Cancer Center School of Medicine University of California San Diego La Jolla CA United States

molecular pathology, such as high-throughput genomic and proteomic profiling, identifies precise disease targets from biopsies but require tissue dissociation, losing valuable histologic and spatial context. Emerging spatial multi-omic technologies now enable multiplexed visualization of genomic, proteomic, and epigenomic targets within a single tissue slice, eliminating the need for labeling multiple adjacent slices. Although early work focused on RNA (spatial transcriptomics), spatial technologies can now concurrently capture DNA, genome accessibility, histone modifications, and proteins with spatially-resolved single-cell resolution. This review outlines the principles, advantages, limitations, and potential for spatial technologies to advance dermatologic research. By jointly profiling multiple molecular channels, spatial multiomics enables novel studies of copy number variations, clonal heterogeneity, and enhancer dysregulation, replete with spatial context, illuminating the skin's complex heterogeneity. © 2024 The Authors

关键词： Dermatopathology Digital pathology Multiomics Multiplexed imaging Spatial sequencing

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BPS2025 - Dynamic and multicolor electron microscopy

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Biophysical Journal 2025年第3期124卷 310a-310a页

作者： Maxim B. Prigozhin Department of Molecular and Cellular Biology and Applied Physics Program Harvard University Cambridge MA USA

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N-glycan-dependent protein maturation and quality control in the ER

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Nature Reviews molecular Cell biology 2025年 1-14页

作者： Guay, Kevin P. Chou, Wen-Chuan Canniff, Nathan P. Paul, Kylie B. Hebert, Daniel N. Program in Molecular and Cellular Biology University of Massachusetts Amherst MA United States Department of Biochemistry and Molecular Biology University of Massachusetts Amherst MA United States

The vast majority of proteins that traverse the mammalian secretory pathway become N-glycosylated in the endoplasmic reticulum (ER). The bulky glycan protein modifications, which are conserved in fungi and humans, act as maturation and quality-control tags. In this Review, we discuss findings published in the past decade that have rapidly expanded our understanding of the transfer and processing of N-glycans, as well as their role in protein maturation, quality control and trafficking in the ER, facilitated by structural insights into the addition of N-glycans by the oligosaccharyltransferases A and B (OST-A and OST-B). These findings suggest that N-glycans serve as reporters of the folding status of secretory proteins as they traverse the ER, enabling the lectin chaperones to guide their maturation. We also explore how the emergence of co-translational glycosylation and the expansion of the glycoproteostasis network in metazoans has expanded the role of N-glycans in early protein-maturation events and quality control. © Springer Nature Limited 2025.

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Alkaline lignin from Clarisia racemosa wood: antioxidant, immunomodulatory, and schistosomicidal activities, and its use as an excipient in praziquantel release

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International Journal of Biological Macromolecules 2025年 310卷 143372页

作者： Cavalcante, Lucas Andrade Oliveira de Oliveira Moraes Miranda, Josué Filipe Silva, Maria Gabriela Cavalcanti Pereira, Maria Julha Felix Marques, Diego Santa Clara do Nascimento Junior, Agrinaldo Jacinto de Oliveira, Ila Maranhão Maia, Rafael Trindade de Lima, Maria Carmo Alves de Lima Aires, André da Cruz Filho, Iranildo José Department of Tropical Medicine Federal University of Pernambuco 50670-901 Brazil Department of Antibiotics Laboratory of Chemistry and Therapeutic Innovation Federal University of Pernambuco 50670-901 Brazil Federal Institute of Education Science and Technology of Brasília - Campus Planaltina 73 380-900 Brazil Center for Sustainable Development of the Semiarid Region Federal University of Campina Postgraduate Program in Natural Sciences and Biotechnology at UFCG and the Postgraduate Program in Cellular and Molecular Biology at UFPB Brazil

Lignins are versatile macromolecules with a wide range of applications across various industrial sectors. In this groundbreaking study, alkaline lignin was successfully isolated and characterized from the wood of Clarisia racemosa, a tree of significant economic value in the Amazon timber industry. Lignin extraction was performed through acid extraction followed by delignification. Characterization of the isolated lignin revealed its GSH-type structure, along with thermal stability and low molecular weight. Subsequent investigations focused on the lignin's biological properties. In vitro, the assays demonstrated its potent antioxidant activity, effectively scavenging free radicals. Lignin also exhibited low toxicity and notable immunomodulatory properties, promoting the proliferation and activation of immune cells. Furthermore, it's in vitro schistosomicidal activity against Schistosoma mansoni was confirmed, with scanning electron microscopy revealing significant effects on the parasite. Finally, the study verified that lignin from Clarisia racemosa is a promising excipient for the controlled release of praziquantel, highlighting its potential in the formulation of ecologically and economically sustainable tablets. This research contributes to the innovative utilization of lignin in the development of environmentally friendly and cost-effective pharmaceutical products. © 2025

关键词： Biomaterial Lignin Schistosoma mansoni

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