Article
Cell Biology
Mariana Borsa, Sandrine Obba, Felix C. Richter, Hanlin Zhang, Thomas Riffelmacher, Joana Carrelha, Ghada Alsaleh, Sten Eirik W. Jacobsen, Anna Katharina Simon
Summary: This study investigates the importance of autophagy in stem cells and finds that autophagy deficiency leads to stem cell loss and bone marrow failure, while inhibition of MTOR can rescue this loss and improve stem cell function.
Review
Nutrition & Dietetics
Siyuan Sun, Yingxue Han, Yumei Lei, Yifei Yu, Yanbin Dong, Juan Chen
Summary: This review comprehensively summarizes the intrinsic factors involved in the regulation of hematopoietic stem cells (HSCs), including RNA-binding protein, modulators in epigenetics, and enhancer-promotor-mediated transcription. It also explores their roles in bone marrow transplantation therapies and autoimmune diseases. Additionally, it discusses the effects of high-fat diets and nutrients (such as vitamins, amino acids, probiotics, and prebiotics) on HSC regulation, providing valuable insights for future HSC research.
Article
Medicine, Research & Experimental
Na Yin, Gang Jin, Yuying Ma, Hanfei Zhao, Guangyue Zhang, Ming O. Li, Min Peng
Summary: This study demonstrates the critical role of nutrient mTORC1 signaling in maintaining hematopoietic stem cell (HSC) homeostasis. Loss of the mTORC1 regulators SZT2 and TSC1 leads to rapid HSC depletion and the synergistic effect of these losses significantly increases mTORC1 activity and ROS production, further depleting HSCs.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Cell Biology
Biljana Blagojevic, Fadi Almouhanna, Gernot Poschet, Stefan Woelfl
Summary: This study investigates the regulation of Sestrin2 and its role in cancer cells under amino acid deprivation. The findings suggest that Sestrin2 regulation is influenced by a complex interplay of oxidative, energetic, and nutritional stress. Furthermore, essential and non-essential amino acids have different effects on Sestrin2 regulation, which could serve as an indicator of cellular vulnerability. Finally, the study shows that GCN2-ATF4-mediated Sestrin2 induction inhibits mTORC1 activity only in cells unable to replenish amino acids through metabolic reprogramming.
Article
Multidisciplinary Sciences
Akihiro Tame, Tadashi Maruyama, Tetsuro Ikuta, Yoshihito Chikaraishi, Nanako O. Ogawa, Masashi Tsuchiya, Kiyotaka Takishita, Miwako Tsuda, Miho Hirai, Yoshihiro Takaki, Naohiko Ohkouchi, Katsunori Fujikura, Takao Yoshida
Summary: Controlling mTORC1 in mussels helps retain symbionts for nutrition, but the digestion of symbionts is triggered when the symbiotic bacteria's energy source is depleted.
Review
Cell Biology
Jiajun Zhu, Hua Wang, Xuejun Jiang
Summary: In this review, Zhu et al. provide an overview of the current understanding of how mTORC1 activity is connected to cell death regulation through metabolic and signaling pathways. The authors focus on the interaction between mTORC1 and ferroptosis, an iron-dependent cell death program, and highlight the importance of further investigating the interplay between mTORC1 and cell death pathways.
JOURNAL OF CELL BIOLOGY
(2022)
Review
Agriculture, Dairy & Animal Science
Shizhe Zhang, Xueyan Lin, Qiuling Hou, Zhiyong Hu, Yun Wang, Zhonghua Wang
Summary: mTORC1 integrates various signal inputs to regulate cell growth and proliferation, with amino acids having a unique pathway of modulation. Recent advances have elucidated the transmission mechanism of amino acid signals upstream of mTORC1.
Review
Immunology
Carsten Riether
Summary: Adult bone marrow hematopoietic stem cells (HSCs) maintain their function through interactions with regulatory T cells (Tregs). In leukemia, these regulatory mechanisms are disrupted, leading to compromised treatment outcomes.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Geriatrics & Gerontology
Julia L. Sheffler, Valeria Burchard, Scott Pickett
Summary: Adverse childhood experiences (ACEs) are associated with sleep impairment, but little is known about modifiable factors that may ameliorate this relationship, such as adaptive emotion regulation (ER) skills. The study found that positive reappraisal and refocusing on planning, two types of ER skills, moderated the relationship between ACEs and sleep quality in older adults.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Jagannath Misra, Michael J. Holmes, Emily T. Mirek, Michael Langevin, Hyeong-Geug Kim, Kenneth R. Carlson, Malcolm Watford, X. Charlie Dong, Tracy G. Anthony, Ronald C. Wek
Summary: Proper regulation of the Integrated stress response (ISR) and mTORC1 signaling is crucial for cell adaptation to amino acid starvation. Halofuginone (HF) inhibits aminoacylation of tRNA(Pro) and increases free amino acids, promoting translation of genes involved in protein biogenesis. Deletion of GCN2 reduces cell survival to HF, while inhibition of mTORC1 provides protection.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Laura Mediani, Francesco Antoniani, Veronica Galli, Jonathan Vinet, Arianna Dorotea Carra, Ilaria Bigi, Vadreenath Tripathy, Tatiana Tiago, Marco Cimino, Giuseppina Leo, Triana Amen, Daniel Kaganovich, Cristina Cereda, Orietta Pansarasa, Jessica Mandrioli, Priyanka Tripathi, Dirk Troost, Eleonora Aronica, Johannes Buchner, Anand Goswami, Jared Sterneckert, Simon Alberti, Serena Carra
Summary: Hsp90 is essential for SG dissolution by binding and stabilizing DYRK3, thus linking stress adaptation and cell growth through regulating condensate disassembly and translation restoration.
Review
Agriculture, Dairy & Animal Science
E. A. Posey, T. A. Davis
Summary: Despite advances in nutritional support, low birth weight and early-weaned piglets still experience reduced extrauterine growth. Recent studies have increased our understanding of the role of nutrition in skeletal muscle growth in piglets and have shown that insulin and amino acids, especially leucine, stimulate protein synthesis and lean growth through different pathways involving mTORC1. However, skeletal muscle in low birth weight piglets shows a dampened anabolic response.
Article
Cell & Tissue Engineering
Zenghua Lin, Maile K. Hollinger, Zhijie Wu, Wanling Sun, Kaylind Batey, Jisoo Kim, Jichun Chen, Xingmin Feng, Neal S. Young
Summary: It was found that sirolimus enhanced the regeneration of hematopoietic stem and progenitor cells in mice exposed to sublethal total body irradiation and other regenerative stressors. The effects were associated with increased expression of hematopoietic genes, reduced DNA damage and clearance of cellular reactive oxygen species. Sirolimus also showed potential clinical applications for the treatment and prevention of hematopoietic injury.
Review
Endocrinology & Metabolism
Han Fang, Kirsten P. Stone, Laura A. Forney, Desiree Wanders, Thomas W. Gettys
Summary: FGF21 is a potent metabolic regulator that is influenced by dietary protein, specifically methionine restriction, leading to effects on energy balance, adipose tissue remodeling, and insulin sensitivity. Liver functions as a sentinel to detect changes in dietary amino acid composition and mobilizes FGF21 as a key element of the homeostatic response. Therapeutic diets could be developed to increase FGF21 levels through nutritional modulation for sustained biological effects.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Biology
Longfei Gao, Matthew Decker, Haidee Chen, Lei Ding
Summary: This study identified the liver, rather than the bone marrow, as the main source of THPO protein after myeloablation. Mice with conditional Thpo deletion from hepatocytes showed significant defects in HSC regeneration and hematopoietic rebound after myeloablation, highlighting the essential role of systemic THPO from the liver in supporting hematologic recovery under myeloablative stress conditions.
Article
Hematology
Mihir Gupta, Evan J. Burns, Nicholas Z. Georgantas, Julia Thierauf, Naema Nayyar, Amanda Gordon, SooAe S. Jones, Michelle Pisapia, Ying Sun, Ryan P. Burns, Jose Velarde, Justin T. Jordan, Matthew J. Frigault, Brian V. Nahed, Pamela S. Jones, Fred G. Barker, William T. Curry, Rajiv Gupta, Tracy T. Batchelor, Javier M. Romero, Priscilla K. Brastianos, Hetal D. Marble, Maria Martinez-Lage, Kensuke Tateishi, Jochen K. Lennerz, Jorg Dietrich, Daniel P. Cahill, Bob S. Carter, Ganesh M. Shankar
Summary: Diagnosing PCNSL often requires neurosurgical biopsy due to low yield of CSF studies. A multiplexed genotyping assay was designed to facilitate rapid and accurate diagnosis of PCNSL. This targeted genotyping approach helps reduce diagnostic and treatment delays in PCNSL.
Correction
Multidisciplinary Sciences
Naama Kanarek, Heather R. Keys, Jason R. Cantor, Caroline A. Lewis, Sze Ham Chan, Tenzin Kunchok, Monther Abu-Remaileh, Elizaveta Freinkman, Lawrence D. Schweitzer, David M. Sabatini
Article
Oncology
Joshua K. Sabari, Vamsidhar Velcheti, Kazuhide Shimizu, Matthew R. Strickland, Rebecca S. Heist, Mohini Singh, Naema Nayyar, Anita Giobbie-Hurder, Subba R. Digumarthy, Justin F. Gainor, Anant P. Rajan, Edwin Nieblas-Bedolla, Aaron C. Burns, Jill Hallin, Peter Olson, James G. Christensen, Sylvia C. Kurz, Priscilla K. Brastianos, Hiroaki Wakimoto
Summary: Patients with KRAS-mutant NSCLC have a high propensity to develop brain metastases. Adagrasib has shown penetration into the cerebrospinal fluid and demonstrated antitumor activity in multiple preclinical models, supporting its potential clinical activity in the brain for patients with KRASG12C-mutant NSCLC and untreated brain metastases.
CLINICAL CANCER RESEARCH
(2022)
Article
Multidisciplinary Sciences
Priscilla K. Brastianos, Albert E. Kim, Anita Giobbie-Hurder, Eudocia Quant Lee, Nancy Wang, April F. Eichler, Ugonma Chukwueke, Deborah A. Forst, Isabel C. Arrillaga-Romany, Jorg Dietrich, Zachary Corbin, Jennifer Moliterno, Joachim Baehring, Michael White, Kevin W. Lou, Juliana Larson, Magali A. de Sauvage, Kathryn Evancic, Joana Mora, Naema Nayyar, Jay Loeffler, Kevin Oh, Helen A. Shih, William T. Curry, Daniel P. Cahill, Fred G. Barker, Elizabeth R. Gerstner, Sandro Santagata
Summary: In a phase 2 clinical trial, pembrolizumab, a PD-1 inhibitor, demonstrated safety and efficacy in patients with high-grade meningiomas. The study achieved its primary endpoint of 6 months progression-free survival and showed promising efficacy in a subset of these tumors. Further research is needed to identify the biological factors that drive response to immune-based therapies in meningioma.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Marta Barradas, Adrian Plaza, Gonzalo Colmenarejo, Iolanda Lazaro, Luis Filipe Costa-Machado, Roberto Martin-Hernandez, Victor Mico, Jose Luis Lopez-Aceituno, Jesus Herranz, Cristina Pantoja, Hector Tejero, Alberto Diaz-Ruiz, Fatima Al-Shahrour, Lidia Daimiel, Viviana Loria-Kohen, Ana Ramirez de Molina, Alejo Efeyan, Manuel Serrano, Oscar J. Pozo, Aleix Sala-Vila, Pablo J. Fernandez-Marcos
Summary: The study shows that fasting can provide protection from chemotherapy-associated toxicity. They found that the profile of fatty acids in erythrocyte membranes and gene expression in peripheral blood mononuclear cells are associated with the benefits of fasting during cancer treatment in mice and patients.
NATURE COMMUNICATIONS
(2022)
Review
Nutrition & Dietetics
Jaehun Jeong, Hyung-Sik Kim, Dongjun Lee, Kihun Kim, Yun-Hak Kim
Summary: Through a systematic review and meta-analysis, this study identified dietary patterns and food items associated with the risk of periodontal disease, which can potentially contribute to lowering the incidence of the disease.
Article
Multidisciplinary Sciences
Giorgia Di Lorenzo, Francescopaolo Iavarone, Marianna Maddaluno, Ana Belen Plata-Gomez, Simone Aureli, Camila Paz Quezada Meza, Laura Cinque, Alessandro Palma, Alessio Reggio, Carmine Cirillo, Francesca Sacco, Alexandra Stolz, Gennaro Napolitano, Oriano Marin, Lorenzo A. Pinna, Maria Ruzzene, Vittorio Limongelli, Alejo Efeyan, Paolo Grumati, Carmine Settembre
Summary: Selective degradation of the endoplasmic reticulum (ER) via autophagy is initiated by ER-phagy receptors, such as FAM134C, which is activated by phosphorylation by CK2 during starvation. This study also reveals the regulatory role of mTORC1 in FAM134C phosphorylation.
Review
Biochemistry & Molecular Biology
Yurena Vivas-Garcia, Alejo Efeyan
Summary: This article discusses the molecular switches that control B-cell metabolism and fuel utilization, as well as the impact of these dynamic metabolic adaptations on B cells throughout the different phases of the humoral response.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Letter
Oncology
Jayoung Kim, Hansong Lee, Chae Mi Hong, Ji Ho Nam, Hye Ju Yeo, Woo Hyun Cho, Hyung-Sik Kim, Changwan Hong, Yun Hak Kim, Dongjun Lee
CANCER COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Bo-Young Kim, Yonghae Son, Byoung Joon Kim, Sung Woon Chung, Dongjun Lee, Seong-Kug Eo, Koanhoi Kim
Summary: The abundance of 7-oxysterols in atherosclerotic lesions leads to elevated expression of CD14 in monocytic cells. In this study, we investigated the effects of three atheroma-relevant 7-oxysterols on CD14 levels in THP-1 cells. The results showed that 7-α-hydroxycholesterol had the strongest induction of CD14 expression and enhanced monocytic cell responses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Philipp Karschnia, Sylvia C. Kurz, Priscilla K. Brastianos, Sebastian F. Winter, Amanda Gordon, Sooae Jones, Michelle Pisapia, Naema Nayyar, Joerg-Christian Tonn, Tracy T. Batchelor, Scott R. Plotkin, Jorg Dietrich
Summary: This study investigates the association between MTHFR polymorphisms and the risk of leukoencephalopathy, and finds that the 1298A -> C genotype is associated with an increased frequency and severity of leukoencephalopathy.
Article
Biotechnology & Applied Microbiology
Lara P. Fernandez, Nerea Deleyto-Seldas, Gonzalo Colmenarejo, Alba Sanz, Sonia Wagner, Ana Belen Plata-Gomez, Monica Gomez-Patino, Susana Molina, Isabel Espinosa-Salinas, Elena Aguilar-Aguilar, Sagrario Ortega, Osvaldo Grana-Castro, Viviana Loria-Kohen, Pablo J. Fernandez-Marcos, Alejo Efeyan, Ana Ramirez de Molina
Summary: This study identified a SNP, rs2291007, in the conserved region of the 3'UTR of the FNIP2 gene that is associated with multiple leanness parameters. The SNP affects FNIP2 mRNA levels and leads to decreased adiposity and increased leanness in both human volunteers and mice. FNIP2 expression is an important contributor to body mass index prediction.
Article
Oncology
Christopher Alvarez-Breckenridge, Samuel C. Markson, Jackson H. Stocking, Naema Nayyar, Matt Lastrapes, Matthew R. Strickland, Albert E. Kim, Magali de Sauvage, Ashish Dahal, Juliana M. Larson, Joana L. Mora, Andrew W. Navia, Robert H. Klein, Benjamin M. Kuter, Corey M. Gill, Mia Bertalan, Brian Shaw, Alexander Kaplan, Megha Subramanian, Aarushi Jain, Swaminathan Kumar, Husain Danish, Michael White, Osmaan Shahid, Kristen E. Pauken, Brian C. Miller, Dennie T. Frederick, Christine Hebert, McKenzie Shaw, Maria Martinez-Lage, Matthew Frosch, Nancy Wang, Elizabeth Gerstner, Brian Nahed, William T. Curry, Bob Carter, Daniel P. Cahill, Genevieve Marie Boland, Benjamin Izar, Michael A. Davies, Arlene H. Sharpe, Mario L. Suva, Ryan J. Sullivan, Priscilla K. Brastianos, Scott L. Carter
Summary: This study investigates the tumor microenvironment (TME) of melanoma-derived brain metastases (MBM) and its correlation with immune checkpoint inhibitors (ICI) using single-cell RNA sequencing and T-cell receptor clonotyping. The results suggest that MBM TME exhibits phenotypic heterogeneity and that the phenotype, clonotype, and overall number of T cells infiltrating MBM are associated with response to ICI.
CANCER IMMUNOLOGY RESEARCH
(2022)
Article
Endocrinology & Metabolism
Yu Ting Ong, Jorge Andrade, Max Armbruster, Chenyue Shi, Marco Castro, Ana S. H. Costa, Toshiya Sugino, Guy Eelen, Barbara Zimmermann, Kerstin Wilhelm, Joseph Lim, Shuichi Watanabe, Stefan Guenther, Andre Schneider, Francesca Zanconato, Manuel Kaulich, Duojia Pan, Thomas Braun, Holger Gerhardt, Alejo Efeyan, Peter Carmeliet, Stefano Piccolo, Ana Rita Grosso, Michael Potente
Summary: Ong et al. report on the intersection of YAP/TAZ and mTORC1 signalling in endothelial cells, showing their role in regulating nutrient acquisition and vascular growth. YAP/TAZ promote angiogenesis by stimulating the import of amino acids and other essential nutrients, leading to mTORC1 activation. This study highlights the importance of coordinated nutrient fluxes in the vasculature.
Article
Clinical Neurology
Shingo Fujio, Tareq A. Juratli, Tomoko Takajo, Kazunori Arita, Yushi Nagano, Koji Yoshimoto, Naema Nayyar, William T. Curry, Maria Martinez-Lage, Daniel P. Cahill, Fred G. Barker, Priscilla K. Brastianos
Summary: TERTp mutations are not associated with tumor relapse in craniopharyngiomas, and TERTp methylation does not correlate with pathological subtype, genotype, or tumor aggressiveness in this study.
NEUROLOGIA MEDICO-CHIRURGICA
(2021)