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JCI Insight: March 22, 2022, issue

Read full issue (Volume 7, issue 6)

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On the cover:

Heckel et al. report that excess dietary lipids sensed by free fatty acid receptor 1 restrain autophagy and energy metabolism in photoreceptors in mice, contributing to pathological neovascularization. The cover image shows confocal images of 3D reconstructed lectin-stained vessels of a very-low-density lipoprotein receptor–deficient mouse retina.
Perspective
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Pearls of wisdom for aspiring physician-scientist residency applicants and program directors
Emily J. Gallagher, Don C. Rockey, Christopher D. Kontos, Jatin M. Vyas, Lawrence F. Brass, Patrick J. Hu, Carlos M. Isales, Olujimi A. Ajijola, W. Kimryn Rathmell, Paul R. Conlin, Robert A. Baiocchi, Barbara I. Kazmierczak, Myles H. Akabas, and Christopher S. Williams
Gaps between college and starting an MD-PhD program are adding years to physician-scientist training time
Lawrence F. Brass, Reiko Maki Fitzsimonds, and Myles H. Akabas
New insights into an old question: can the MD-PhD physician-scientist pipeline be improved?
Ronald J. Koenig
Predoctoral MD-PhD grants as indicators of future NIH funding success
Shohini Ghosh-Choudhary, Neil Carleton, S. Mehdi Nouraie, Corrine R. Kliment, and Richard A. Steinman
Research articles
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Clinical Medicine
A 4-week high-AGE diet does not impair glucose metabolism and vascular function in obese individuals
Armand M.A. Linkens, Alfons J.H.M. Houben, Petra M. Niessen, Nicole E.G. Wijckmans, Erica E.C. de Goei, Mathias D.G. Van den Eynde, Jean L.J.M. Scheijen, Marjo P.H. van den Waarenburg, Andrea Mari, Tos T.J.M. Berendschot, Lukas Streese, Henner Hanssen, Martien C.J.M. van Dongen, Christel C.J.A.W. van Gool, Coen D.A. Stehouwer, Simone J.M.P. Eussen, and Casper G. Schalkwijk
Clinical Medicine
Neurofilament proteins as a potential biomarker in chemotherapy-induced polyneuropathy
Petra Huehnchen, Christian Schinke, Nikola Bangemann, Adam D. Dordevic, Johannes Kern, Smilla K. Maierhof, Lois Hew, Luca Nolte, Peter Körtvelyessy, Jens C. Göpfert, Klemens Ruprecht, Christopher J. Somps, Jens-Uwe Blohmer, Jalid Sehouli, Matthias Endres, and Wolfgang Boehmerle
Clinical Medicine
Evidence of islet CADM1-mediated immune cell interactions during human type 1 diabetes
Chandan Sona, Yu-Te Yeh, Andreas Patsalos, Laszlo Halasz, Xin Yan, Natalia L. Kononenko, Laszlo Nagy, and Matthew N. Poy
Cilia proteins are biomarkers of altered flow in the vasculature
Ankan Gupta, Karthikeyan Thirugnanam, Madhan Thamilarasan, Ashraf M. Mohieldin, Hadeel T. Zedan, Shubhangi Prabhudesai, Meghan R. Griffin, Andrew D. Spearman, Amy Pan, Sean P. Palecek, Huseyin C. Yalcin, Surya M. Nauli, Kevin R. Rarick, Rahima Zennadi, and Ramani Ramchandran
CFTR bearing variant p.Phe312del exhibits function inconsistent with phenotype and negligible response to ivacaftor
Karen S. Raraigh, Kathleen C. Paul, Jennifer L. Goralski, Erin N. Worthington, Anna V. Faino, Stanley Sciortino, Yiting Wang, Melis A. Aksit, Hua Ling, Derek L. Osorio, Frankline M. Onchiri, Shivani U. Patel, Christian A. Merlo, Kristina Montemayor, Ronald L. Gibson, Natalie E. West, Amita Thakerar, Robert J. Bridges, David N. Sheppard, Neeraj Sharma, and Garry R. Cutting
Triglyceride-derived fatty acids reduce autophagy in a model of retinal angiomatous proliferation
Emilie Heckel, Gael Cagnone, Tapan Agnihotri, Bertan Cakir, Ashim Das, Jin Sung Kim, Nicholas Kim, Geneviève Lavoie, Anu Situ, Sheetal Pundir, Ye Sun, Florian Wünnemann, Kerry A. Pierce, Courtney Dennis, Grant A. Mitchell, Sylvain Chemtob, Flavio A. Rezende, Gregor Andelfinger, Clary B. Clish, Philippe P. Roux, Przemyslaw Sapieha, Lois E.H. Smith, and Jean-Sébastien Joyal
CFTR-mediated monocyte/macrophage dysfunction revealed by cystic fibrosis proband-parent comparisons
Xi Zhang, Camille M. Moore, Laura D. Harmacek, Joanne Domenico, Vittobai Rashika Rangaraj, Justin E. Ideozu, Jennifer R. Knapp, Katherine J. Woods, Stephanie Jump, Shuang Jia, Jeremy W. Prokop, Russell Bowler, Martin J. Hessner, Erwin W. Gelfand, and Hara Levy
Transcriptional analysis of lung fibroblasts identifies PIM1 signaling as a driver of aging-associated persistent fibrosis
Tho X. Pham, Jisu Lee, Jiazhen Guan, Nunzia Caporarello, Jeffrey A. Meridew, Dakota L. Jones, Qi Tan, Steven K. Huang, Daniel J. Tschumperlin, and Giovanni Ligresti
WEE1 kinase is a therapeutic vulnerability in CIC-DUX4 undifferentiated sarcoma
Rovingaile Kriska M. Ponce, Nicholas J. Thomas, Nam Q. Bui, Tadashi Kondo, and Ross A. Okimoto
Critical role of Znhit1 for postnatal heart function and vacuolar cardiomyopathy
Yingchao Shi, Wenli Fan, Mingjie Xu, Xinhua Lin, Wukui Zhao, and Zhongzhou Yang
Current opportunities:
Reach a wide community of physician-scientists, biomedical scientists, and clinicians through the ASCI's job board.
Long noncoding RNA Gm31629 protects against mucosal damage in experimental colitis via YB-1/E2F pathway
Xu Feng, Ye Xiao, Jian He, Mi Yang, Qi Guo, Tian Su, Yan Huang, Jun Yi, Chang-Jun Li, Xiang-Hang Luo, Xiao-Wei Liu, and Hai-Yan Zhou
Regional variability and genotypic and pharmacodynamic effects on PrP concentration in the CNS
Meredith A. Mortberg, Hien T. Zhao, Andrew G. Reidenbach, Juliana E. Gentile, Eric Kuhn, Jill O’Moore, Patrick M. Dooley, Theresa R. Connors, Curt Mazur, Shona W. Allen, Bianca A. Trombetta, Alison McManus, Matthew R. Moore, Jiewu Liu, Deborah E. Cabin, Holly B. Kordasiewicz, Joel Mathews, Steven E. Arnold, Sonia M. Vallabh, and Eric Vallabh Minikel
T cell response to intact SARS-CoV-2 includes coronavirus cross-reactive and variant-specific components
Lichen Jing, Xia Wu, Maxwell P. Krist, Tien-Ying Hsiang, Victoria L. Campbell, Christopher L. McClurkan, Sydney M. Favors, Lawrence A. Hemingway, Charmie Godornes, Denise Q. Tong, Stacy Selke, Angela C. LeClair, Chu-Woo Pyo, Daniel E. Geraghty, Kerry J. Laing Anna Wald, Michael Gale Jr., and David M. Koelle
CMV-associated T cell and NK cell terminal differentiation does not affect immunogenicity of ChAdOx1 vaccination
Hannah R. Sharpe, Nicholas M. Provine, Georgina S. Bowyer, Pedro Moreira Folegatti, Sandra Belij-Rammerstorfer, Amy Flaxman, Rebecca Makinson, Adrian V.S. Hill, Katie J. Ewer, Andrew J. Pollard, Paul Klenerman, Sarah Gilbert, and Teresa Lambe
Trastuzumab/pertuzumab combination therapy stimulates antitumor responses through complement-dependent cytotoxicity and phagocytosis
Li-Chung Tsao, Erika J. Crosby, Timothy N. Trotter, Junping Wei, Tao Wang, Xiao Yang, Amanda N. Summers, Gangjun Lei, Christopher A. Rabiola, Lewis A. Chodosh, William J. Muller, Herbert Kim Lyerly, and Zachary C. Hartman
Modulation of gentamicin-induced acute kidney injury by myo-inositol oxygenase via the ROS/ALOX-12/12-HETE/GPR31 signaling pathway
Isha Sharma, Yingjun Liao, Xiaoping Zheng, and Yashpal S. Kanwar
CSF1/CSF1R signaling mediates malignant pleural effusion formation
Chrysavgi N. Kosti, Photene C. Vaitsi, Apostolos G. Pappas, Marianthi P. Iliopoulou, Katherina K. Psarra, Sophia F. Magkouta, and Ioannis T. Kalomenidis
Notch-mediated Ephrin signaling disrupts islet architecture and β cell function
Alberto Bartolomé, Nina Suda, Junjie Yu, Changyu Zhu, Jinsook Son, Hongxu Ding, Andrea Califano, Domenico Accili, and Utpal B. Pajvani
Human antibodies against noncircumsporozoite proteins block Plasmodium falciparum parasite development in hepatocytes
Amanda Fabra-García, Annie S.P. Yang, Marije C. Behet, Zen Yap, Youri van Waardenburg, Swarnendu Kaviraj, Kjerstin Lanke, Geert-Jan van Gemert, Matthijs M. Jore, Teun Bousema, and Robert W. Sauerwein
Targeting IRE1 endoribonuclease activity alleviates cardiovascular lesions in a murine model of Kawasaki disease vasculitis
Stefanie Marek-Iannucci, Asli D. Yildirim, Syed M. Hamid, Asli B. Ozdemir, Angela C. Gomez, Begüm Kocatürk, Rebecca A. Porritt, Michael C. Fishbein, Takao Iwawaki, Magali Noval Rivas, Ebru Erbay, and Moshe Arditi
Corrigendum
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miR–9-5p regulates immunometabolic and epigenetic pathways in β-glucan–trained immunity via IDH3α
Haibo Su, Zhongping Liang, ShuFeng Weng, Chaonan Sun, Jiaxin Huang, TianRan Zhang, Xialian Wang, Shanshan Wu, Zhi Zhang, Yiqi Zhang, Qing Gong, and Ying Xu

In-Press Previews

Published March 8, 2022, at 12:00 PM EST
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Research
Characterization of disease-propagating stem cells responsible for myeloproliferative neoplasm-blast phase
Xiaoli Wang, Raajit K. Rampal, Cing Siang Hu, Joseph Tripodi, Noushin Farnoud, Bruce Petersen, Michael R. Rossi, Minal Patel, Erin McGovern, Vesna Najfeld, Camelia Iancu-Rubin, Min Lu, Andrew Davis, Marina Kremyanskaya, Rona Singer Weinberg, John Mascarenhas, Ronald Hoffman
Published March 10, 2022, at 12:00 PM EST
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Research
Heterogeneity and clonality of kidney-infiltrating T cells in murine lupus nephritis
Shuchi Smita, Maria Chikina, Mark J. Shlomchik, Jeremy S. Tilstra
Research
Lymph node CXCR5+ NK cells associate with control of chronic SHIV infection
Sheikh Abdul Rahman, James Billinglsley, Ashish Arunkumar Sharma, Tiffany M. Styles, Sakthivel Govindaraj, Uma Shanmugasundaram, Hemalatha Babu, Susan Pereira Ribeiro, Syed A. Ali, Gregory K. Tharp, Chris Ibegbu, Stephen Waggoner, R. Paul Johnson, Rafick-Pierre Sékaly, Francois Villinger, Steven E. Bosinger, Rama Rao Amara, Vijayakumar Velu
Published March 15, 2022, at 12:00 PM EDT
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Research
Monoclonal antibody targeting the conserved region of the SARS-CoV-2 spike protein to overcome viral variants
Wan-Ling Wu, Chen-Yi Chiang, Szu-Chia Lai, Chia-Yi Yu, Yu-Ling Huang, Hung-Chun Liao, Ching-Len Liao, Hsin-Wei Chen, Shih-Jen Liu
Research

Rasa3 deficiency minimally impacts thrombopoiesis but promotes severe thrombocytopenia due to integrin-dependent platelet clearance 

Robert H Lee, Dorsaf Ghalloussi, Gabriel L. Harousseau, Joseph P. Kenny, Patrick A. Kramer, Fabienne Proamer, Bernhard Nieswandt, Matthew J. Flick, Christian Gachet, Caterina Casari, Anita Eckly, Wolfgang Bergmeier
Resource and Technical Advance
Single-cell transcriptomics reveals distinct effector profiles of infiltrating T cells in lupus skin and kidney
Garrett S. Dunlap, Allison C. Billi, Xianying Xing, Feiyang Ma, Mitra P. Maz, Lam C. Tsoi, Rachael Wasikowski, Jeffrey B. Hodgin, Johann E. Gudjonsson, J. Michelle Kahlenberg, Deepak A. Rao
Resource and Technical Advance
Reduction of mutant ATXN1 rescues premature death in a conditional SCA1 mouse model
James P. Orengo, Larissa Nitschke, Meike E. van der Heijden, Nicholas A. Ciaburri, Harry T. Orr, Huda Y. Zoghbi
Published March 17, 2022, at 12:00 PM EDT
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Research
14-3-3ζ constrains insulin secretion by regulating mitochondrial function in pancreatic β-cells
Yves Mugabo, Cheng Zhao, Ju Jing Tan, Anindya Ghosh, Scott A. Campbell, Evgenia Fadzeyeva, Frédéric Paré, Siew Siew Pan, Maria Galipeau, Julia Ast, Johannes Broichhagen, David J. Hodson, Erin E. Mulvihill, Sophie Petropoulos, Gareth E. Lim
Clinical Medicine
RAGE has potential pathogenetic and prognostic value in non-intubated hospitalized patients with COVID-19
Katherine D. Wick, Lianne Siegel, James D. Neaton, Cathryn Oldmixon, Jens Lundgren, Robin L. Dewar, H. Clifford Lane, B. Taylor Thompson, Michael A. Matthay
Published March 22, 2022, at 12:00 PM EDT
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Resource and Technical Advance
Whole-transcriptome sequencing-based concomitant detection of viral and human genetic determinants of cutaneous lesions
Amir Hossein Saeidian, Leila Youssefian, Charles Y. Huang, Fahimeh Palizban, Mahtab Naji, Zahra Saffarian, Hamidreza Mahmoudi, Azadeh Goodarzi, Soheila Sotoudeh, Fatemeh Vahidnezhad, Maliheh Amani, Narjes Tavakoli, Ali Ajami, Samaneh Mozafarpoor, Mehrdad Teimoorian, Saeed Dorgaleleh, Sima Shokri, Mohammad Shenagari, Nima Abedi, Sirous Zeinali, Paolo Fortina, Vivien Béziat, Emmanuelle Jouanguy, Jean-Laurent Casanova, Jouni Uitto, Hassan Vahidnezhad
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