Article
Biology
Timothy W. Church, Parul Tewatia, Saad Hannan, Joao Antunes, Olivia Eriksson, Trevor G. Smart, Jeanette Hellgren Kotaleski, Matthew G. Gold
Summary: The study found that AKAP79 enhances calcineurin activity, which leads to the suppression of PKA without altering cAMP levels. This non-canonical mode of PKA regulation may play a role in many other cellular processes.
Article
Multidisciplinary Sciences
Annemarie Steiner, Katja Hrovat-Schaale, Ignazia Prigione, Chien-Hsiung Yu, Pawat Laohamonthonkul, Cassandra R. Harapas, Ronnie Ren Jie Low, Dominic De Nardo, Laura F. Dagley, Michael J. Mlodzianoski, Kelly L. Rogers, Thomas Zillinger, Gunther Hartmann, Michael P. Gantier, Marco Gattorno, Matthias Geyer, Stefano Volpi, Sophia Davidson, Seth L. Masters
Summary: Deficiency in COPI complex I may lead to aberrant activation of the STING pathway and inflammatory diseases, with cGAS possibly being the upstream immune sensor driving this process. Targeted inhibition of the cGAS/STING pathway can alleviate inflammation in diseases such as COPA syndrome.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Yutao Liu, Bin Liu, Tingting Xu, Qian Wang, Wendi Li, Jialin Wu, Xiaoyu Zheng, Bin Liu, Ruiying Liu, Xingmei Liu, Xi Guo, Lu Feng, Lei Wang
Summary: The study identifies a fructose uptake system crucial for the growth of Vibrio cholerae in seawater, where fructose concentrations are low. This system may be important for the survival of pandemic V. cholerae in seawater.
NATURE COMMUNICATIONS
(2021)
Article
Urology & Nephrology
Stephen C. Parnell, Archana Raman, Yan Zhang, Emily A. Daniel, Yuqiao Dai, Aditi Khanna, Gail A. Reif, Jay L. Vivian, Timothy A. Fields, Darren P. Wallace
Summary: This study demonstrates that active BRAF is sufficient to induce kidney cyst formation in normal mice and accelerate cystic disease in PKD mice.
KIDNEY INTERNATIONAL
(2022)
Article
Urology & Nephrology
Xiaofang Wang, Li Jiang, Ka Thao, Caroline R. Sussman, Timothy LaBranche, Michael Palmer, Peter C. Harris, G. Stanley McKnight, Klaus P. Hoeflich, Stefanie Schalm, Vicente E. Torres
Summary: Upregulation of cAMP-dependent and cAMP-independent PKA signaling promotes cystogenesis in polycystic kidney disease (PKD). Activation of PKA-I promotes cystogenesis, while its inhibition prevents cyst formation. Inhibition of PKA activity can directly and/or indirectly inhibit multiple pro-proliferative pathways and is protective in vivo.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2022)
Article
Biochemical Research Methods
Crystian Massengill, Landon Bayless-Edwards, Cesar C. Ceballos, Elizabeth R. Cebul, James Cahill, Arpita Bharadwaj, Evan Wilson, Maozhen Qin, Matthew R. Whorton, Isabelle Baconguis, Bing Ye, Tianyi Mao, Haining Zhong
Summary: cAMPFIREs are genetically encoded cAMP sensors suitable for in vivo imaging of cAMP signaling. They exhibit high sensitivity and cell specificity, showing good performance in in vivo imaging.
Article
Multidisciplinary Sciences
Sonia Colombo, Maddalena Collini, Laura D'Alfonso, Giuseppe Chirico, Enzo Martegani
Summary: This study reveals that the Ras/cAMP/PKA pathway plays a crucial role in regulating the response to nutrients' availability and stress in budding yeast. The activity of this pathway leads to noisy oscillations of cAMP levels, which in turn affects the nuclear accumulation of the transcription factor Msn2. Using a sensor, the researchers were able to detect the changes in cAMP concentrations in single yeast cells and observed oscillations under conditions of nutritional stress caused by limiting glucose availability.
Review
Cell Biology
Camille Derderian, Gabriela I. Canales, Jeremy F. Reiter
Summary: The boundaries between cell and developmental biology have dissolved, leading to the emergence of cilia biology which combines different approaches to understand this multifunctional organelle. Cilia play important roles in intercellular communication and their dysfunction can lead to various diseases. This review highlights the signaling mechanism of cilia, their potential as signaling sources, the influence of evolution on ciliary function, and the unresolved questions in cilia research.
DEVELOPMENTAL CELL
(2023)
Article
Biochemistry & Molecular Biology
Heinrich K. Wasner
Summary: Metformin is the main drug for treating type 2 diabetes, and its mechanism of action, although largely unknown, includes the activation of AMP-kinase, reduction of blood glucose levels, inhibition of cyclic AMP synthesis, gluconeogenesis, and increased sensitivity to insulin.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Wenli Yang, William G. Robichaux, Fang C. Mei, Wei Lin, Li Li, Sheng Pan, Mark A. White, Yuan Chen, Xiaodong Cheng
Summary: It has been found that cAMP regulates cellular SUMOylation through Epac1, which also controls the dynamics of cellular condensates. This research provides insights into the molecular mechanism linking cellular stress responses and protein SUMOylation.
Article
Cell Biology
Dan Zhang, Yutong Liu, Yezhang Zhu, Qian Zhang, Hongxing Guan, Shengduo Liu, Shasha Chen, Chen Mei, Chen Chen, Zhiyong Liao, Ying Xi, Songying Ouyang, Xin-Hua Feng, Tingbo Liang, Li Shen, Pinglong Xu
Summary: The non-canonical cGAS-STING pathway, involving the activation of PERK-eIF2 alpha, contributes to mRNA translation and plays a role in cellular senescence and fibrosis. This finding sheds light on the connection between DNA sensing and cellular physiology, and suggests the therapeutic potential of targeting the STING-PERK pathway in fibrotic diseases.
NATURE CELL BIOLOGY
(2022)
Article
Microbiology
Clem Marsilia, Mrinalini Batra, Irina D. Pokrovskaya, Changqi Wang, Dale Chaput, Daria A. Naumova, Vladimir V. Lupashin, Elena S. Suvorova
Summary: This study reveals the expanded function of the conservative Golgi tethering COG complex in T. gondii and identifies additional regulators of transport specific to the parasite, providing insights into the parasite's secretory organelles.
Article
Pharmacology & Pharmacy
Anastasios Lymperopoulos
Summary: This article discusses the research status of cAMP levels in heart diseases, and finds that there is currently no consensus on the levels of cAMP in human failing hearts. However, many studies indicate that cAMP levels are deficient in human failing hearts, suggesting that strategies to increase rather than decrease these levels should be pursued.
EXPERT REVIEW OF CLINICAL PHARMACOLOGY
(2023)
Article
Chemistry, Medicinal
Seung-Joo Yang, Seungje Jeon, Jeong Won Baek, Kwang Min Lee, Chul-Seung Park
Summary: The study demonstrated that thalidomide does not affect the activation of AMPK or the binding between CRBN and the AMPK alpha subunit. The impact of thalidomide on AMPK activity is independent of CRBN expression.
Article
Biochemistry & Molecular Biology
Masahiro Takahara, Akinobu Takaki, Sakiko Hiraoka, Kensuke Takei, Eriko Yasutomi, Shoko Igawa, Shumpei Yamamoto, Shohei Oka, Masayasu Ohmori, Yasushi Yamasaki, Toshihiro Inokuchi, Hideaki Kinugasa, Keita Harada, Heiichiro Udono, Hiroyuki Okada
Summary: Metformin, a drug commonly used for type 2 diabetes, has been found to suppress intestinal inflammation and improve inflammatory bowel disease (IBD) by activating AMP-activated protein kinase (AMPK). This study suggests that AMPK may be a key molecule in regulating mucosal immunity and inflammation, and AMPK-activating drugs like metformin could be potential therapeutic agents for the treatment of IBD.
Article
Clinical Neurology
L. Gonzalez-Mera, G. Ravenscroft, M. Cabrera-Serrano, N. Ermolova, C. Dominguez-Gonzalez, A. Arteche-Lopez, P. Soltanzadeh, F. Evesson, C. Navas, F. Mavillard, J. Clayton, P. Rodrigo, E. Servian-Morilla, S. T. Cooper, L. Waddell, K. Reardon, A. Corbett, A. Hernandez-Lain, A. Sanchez, J. Esteban Perez, C. Paradas-Lopez, E. Rivas-Infante, M. Spencer, N. Laing, M. Olive
Summary: Recessive variants in the CAPN3 gene are the most common cause of autosomal recessive limb girdle muscle dystrophy. However, this study identified five different heterozygous missense variants in the CAPN3 gene associated with an autosomal dominant form of muscular dystrophy in 21 affected individuals. These variants were found to interfere with calpain 3 function in skeletal muscle.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Shambhabi Chatterjee, Teresa Hofer, Alessia Costa, Dongchao Lu, Sandor Batkai, Shashi Kumar Gupta, Emiliano Bolesani, Robert Zweigerdt, Diego Megias, Katrin Streckfuss-Boemeke, Christina Brandenberger, Thomas Thum, Christian Baer
Summary: Telomerase overexpression can serve as a therapeutic strategy for preventing doxorubicin-induced cardiotoxicity, protecting the heart from doxorubicin-induced damage and restoring cardiac function. Telomerase in cells has antioxidant and anti-apoptotic effects, and achieves protection by regulating mitochondrial morphology and function.
Article
Oncology
Alejandra Leivas, Ruth M. Risueno, Alma Guzman, Laura Sanchez-Vega, Manuel Perez, Diego Megias, Lucia Fernandez, Rafael Alonso, Antonio Perez-Martinez, Inmaculada Rapado, Joaquin Martinez-Lopez
Summary: This study suggests that side population cells may represent the stem cell compartment in multiple myeloma, and NK cells have anti-myeloma activity against clonogenic stem cells, potentially leading to new treatment strategies.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Ana Amor Lopez, Marina S. Mazariegos, Alessandra Capuano, Pilar Ximenez-Embun, Marta Hergueta-Redondo, Juan Angel Recio, Eva Munoz, Fatima Al-Shahrour, Javier Munoz, Diego Megias, Roberto Doliana, Paola Spessotto, Hector Peinado
Summary: Studies have shown that melanoma-derived extracellular vesicles (EVs) play a role in lymph node metastasis, with EMILIN-1 being proteolyzed and secreted in small EVs as a mechanism to reduce its intracellular levels and promote metastasis in mouse melanoma lymph node metastatic cells. EMILIN-1 exhibits tumor and metastasis suppressive properties, reducing effective migration, cell viability, primary tumor growth, and metastasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Geriatrics & Gerontology
Lucia Jimenez, Andreia Silva, Giampaolo Calissi, Ines Grenho, Rita Monteiro, Victor Mayoral-Varo, Carmen Blanco-Aparicio, Joaquin Pastor, Victor Bustos, Franz Bracher, Diego Megias, Bibiana Ferreira, Wolfgang Link
Summary: Various compounds including resveratrol, piperlongumine, and harmine were found to induce FOXO activity, with piperlongumine and harmine activating transcription. These compounds were shown to affect FOXO nuclear translocation and inhibiting ROS production, with molecular mechanisms involving DYRK1A inhibition and SIRTs reverting the effects of harmine on FOXO3 activity, independently of PI3K/AKT signaling and CRM1-mediated nuclear export.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Jose Gonzalez-Martinez, Andrzej W. Cwetsch, Javier Gilabert-Juan, Jesus Gomez, Guillermo Garaulet, Paulina Schneider, Guillermo de Carcer, Francisca Mulero, Eduardo Caleiras, Diego Megias, Eva Porlan, Marcos Malumbres
Summary: This study reveals that the centrosomal kinase PLK1 regulates centrosome asymmetry and cell fate in neural progenitors. Loss of PLK1 activity leads to reduced asymmetry and increased expansion of neural progenitors, promoting cortical growth. However, deficiencies in MCPH proteins result in increased centrosome asymmetry and microcephaly.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Chemistry, Multidisciplinary
Joaquim Torra, Felipe Viela, Diego Megias, Begona Sot, Cristina Flors
Summary: CRANAD-2, a fluorogenic curcumin derivative, shows good performance in both stimulated emission depletion (STED) and single-molecule localization microscopy (SMLM) for near-infrared detection and imaging of amyloid aggregates with a resolution range of 45-55 nm. Its versatility and performance make it a powerful tool for near-infrared nanoscopic imaging of amyloids in vitro and in vivo.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Medicine, Research & Experimental
Lucia Zhu, Diana Retana, Pedro Garcia-Gomez, Laura Alvaro-Espinosa, Neibla Priego, Mariam Masmudi-Martin, Natalia Yebra, Lauritz Miarka, Elena Hernandez-Encinas, Carmen Blanco-Aparicio, Sonia Martinez, Cecilia Sobrino, Nuria Ajenjo, Maria-Jesus Artiga, Eva Ortega-Paino, Raul Torres-Ruiz, Sandra Rodriguez-Perales, Riccardo Soffietti, Luca Bertero, Paola Cassoni, Tobias Weiss, Javier Munoz, Juan Manuel Sepulveda, Pedro Gonzalez-Leon, Luis Jimenez-Roldan, Luis Miguel Moreno, Olga Esteban, Angel Perez-Nunez, Aurelio Hernandez-Lain, Oscar Toldos, Yolanda Ruano, Lucia Alcazar, Guillermo Blasco, Jose Fernandez-Alen, Eduardo Caleiras, Miguel Lafarga, Diego Megias, Osvaldo Grana-Castro, Carolina Nor, Michael D. Taylor, Leonie S. Young, Damir Vareslija, Nicola Cosgrove, Fergus J. Couch, Lorena Cusso, Manuel Desco, Silvana Mouron, Miguel Quintela-Fandino, Michael Weller, Joaquin Pastor, Manuel Valiente
Summary: We report a medium-throughput drug-screening platform based on organotypic cultures that evaluates inhibitors against metastases growing in situ. Through this approach applied to brain metastasis, vulnerabilities were identified and a blood-brain barrier permeable HSP90 inhibitor was found to be effective against mouse and human brain metastases. In situ proteomic analysis revealed a novel molecular program in brain metastasis and potential biomarkers of poor prognosis and resistance mechanisms. This study validates METPlatform as a potent resource for metastasis research and personalized management of metastatic disease.
EMBO MOLECULAR MEDICINE
(2022)
Article
Cell Biology
Barbara Martinez-Pastor, Giorgia G. Silveira, Thomas L. Clarke, Dudley Chung, Yuchao Gu, Claudia Cosentino, Lance S. Davidow, Gadea Mata, Sylvana Hassanieh, Jayme Salsman, Alberto Ciccia, Narkhyun Bae, Mark T. Bedford, Diego Megias, Lee L. Rubin, Alejo Efeyan, Graham Dellaire, Raul Mostoslavsky
Summary: Researchers have developed two high-throughput systems for studying DNA repair kinetics and the recruitment of chromatin factors to double-strand breaks. By using a customized ChromORFeome library, they identified the role of PHF20 factor in affecting DNA repair process. These resources can facilitate our understanding and manipulation of DNA repair through genetic perturbations, small-molecule screens, and large-scale analysis.
Article
Rheumatology
Liliana F. Mellor, Nuria Gago-Lopez, Latifa Bakiri, Felix N. Schmidt, Bjorn Busse, Simon Rauber, Maria Jimenez, Diego Megias, Sergio Oterino-Soto, Ricardo Sanchez-Prieto, Sergei Grivennikov, Xinzhu Pu, Julia Oxford, Andreas Ramming, Georg Schett, Erwin F. Wagner
Summary: Keratinocyte-derived S100A9 plays a regulatory role in psoriatic skin and joint disease. In addition, S100A9 and CP have the potential to serve as biomarkers for identifying Ps patients at risk of developing PsA.
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Lucia Jimenez, Carlos Amenabar, Victor Mayoral-Varo, Thomas A. Mackenzie, Maria C. Ramos, Andreia Silva, Giampaolo Calissi, Ines Grenho, Carmen Blanco-Aparicio, Joaquin Pastor, Diego Megias, Bibiana Ferreira, Wolfgang Link
Summary: FOXO proteins play important roles in cancer and aging, and their activity can be regulated through pharmacological manipulation. The study suggests that mTORC2 is the most important second layer kinase negatively regulating FOXO activity.
Article
Oncology
Cristina Montero-Conde, Luis Javier Leandro-Garcia, Angel M. Martinez-Montes, Paula Martinez, Francisco J. Moya, Rocio Leton, Eduardo Gil, Natalia Martinez-Puente, Sonsoles Guadalix, Maria Curras-Freixes, Laura Garcia-Tobar, Carles Zafon, Mireia Jorda, Garcilaso Riesco-Eizaguirre, Patricia Gonzalez-Garcia, Maria Monteagudo, Rafael Torres-Perez, Veronika Mancikova, Sergio Ruiz-Llorente, Manuel Perez-Martinez, Guillermo Pita, Juan Carlos Galofre, Anna Gonzalez-Neira, Alberto Cascon, Cristina Rodriguez-Antona, Diego Megias, Maria A. Blasco, Eduardo Caleiras, Sandra Rodriguez-Perales, Mercedes Robledo
Summary: Comprehensive molecular studies were conducted on thyroid tumors to identify prognostic biomarkers. Telomere-related alterations, especially TERT and TERC, were found in aggressive tumors. Short telomeres led to reorganization in the 5p subtelomeric region, resulting in increased gene upregulation and a more relaxed chromatin configuration in the tumors.
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Article
Cell Biology
Lucia Jimenez, Victor Mayoral-Varo, Carlos Amenabar, Judit Ortega, Joao G. N. Sequeira, Miguel Machuqueiro, Cristiana Mourato, Romano Silvestri, Andrea Angeli, Fabrizio Carta, Claudiu T. Supuran, Diego Megias, Bibiana I. I. Ferreira, Wolfgang Link
Summary: Chromosomal region maintenance 1 (CRM1), also known as Xpo1 and exportin-1, plays a crucial role in nuclear export and has been identified as a potential therapeutic target for viral infections and cancer. Inhibition of CRM1 has shown promise in treating multiple myeloma, but the currently available inhibitor, selinexor, has dose-limiting toxicity. In this study, the researchers developed a CRM1 inhibitor discovery platform and identified an active organoselenium compound.
Article
Multidisciplinary Sciences
S. Mouron, M. J. Bueno, A. Lluch, L. Manso, I Calvo, J. Cortes, J. A. Garcia-Saenz, M. Gil-Gil, N. Martinez-Janez, J. Apala, E. Caleiras, Pilar Ximenez-Embun, J. Munoz, L. Gonzalez-Cortijo, R. Murillo, R. Sanchez-Bayona, J. M. Cejalvo, G. Gomez-Lopez, C. Fustero-Torre, S. Sabroso-Lasa, N. Malats, M. Martinez, A. Moreno, D. Megias, M. Malumbres, R. Colomer, M. Quintela-Fandino
Summary: Precision oncology research is challenging, but phosphoproteomics can help identify factors for predicting response to paclitaxel.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Susana Garcia-Silva, Alberto Benito-Martin, Laura Nogues, Alberto Hernandez-Barranco, Marina S. Mazariegos, Vanesa Santos, Marta Hergueta-Redondo, Pilar Ximenez-Embun, Raghu P. Kataru, Ana Amor Lopez, Cristina Merino, Sara Sanchez-Redondo, Osvaldo Grana-Castro, Irina Matei, Jose Angel Nicolas-Avila, Raul Torres-Ruiz, Sandra Rodriguez-Perales, Lola Martinez, Manuel Perez-Martinez, Gadea Mata, Iwona Kalinowska, Annalisa Saltari, Julia M. Martinez-Gomez, Sabrina A. Hogan, H. Uri Saragovi, Sagrario Ortega, Carmen Garcia-Martin, Jasminka Boskovic, Mitchell P. Levesque, Piotr Rutkowski, Andres Hidalgo, Javier Munoz, Diego Megias, Babak J. Mehrara, David Lyden, Hector Peinado
Summary: Peinado and colleagues demonstrate that melanoma-secreted small extracellular vesicles (sEVs) and NGFR cargo can induce lymphangiogenesis and promote lymph node pre-metastatic niche formation, facilitating melanoma metastasis. Targeting NGFR could potentially prevent this process in pre-clinical settings.