JCI Insight
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JCI Insight: November 2, 2017, issue

Read full issue online (Volume 2, issue 21)
Human regulatory T cells undergo self-inflicted damage via granzyme pathways upon activation
Leakage of granzymes A and B from cytotoxic granules induces self-inflicted damage in activated human regulatory T cells.
Esilida Sula Karreci, Siawosh K. Eskandari, Farokh Dotiwala, Sujit K. Routray, Ahmed T. Kurdi, Jean Pierre Assaker, Pavlo Luckyanchykov, Albana B. Mihali, Omar Maarouf, Thiago J. Borges, Abdullah Alkhudhayri, Kruti R. Patel, Amr Radwan, Irene Ghobrial, Martina McGrath, Anil Chandraker, Leonardo V. Riella, Wassim Elyaman, Reza Abdi, Judy Lieberman, and Jamil Azzi
Combined inhibition of atypical PKC and histone deacetylase 1 is cooperative in basal cell carcinoma treatment
A bioavailable, selective small molecule aPKC inhibitor acts synergistically with the HDAC inhibitor vorinostat in preclinical models of Hedgehog-dependent cancers.
Amar N. Mirza, Micah A. Fry, Nicole M. Urman, Scott X. Atwood, Jon Roffey, Gregory R. Ott, Bin Chen, Alex Lee, Alexander S. Brown, Sumaira Z. Aasi, Tyler Hollmig, Mark A. Ator, Bruce D. Dorsey, Bruce R. Ruggeri, Craig A. Zificsak, Marina Sirota, Jean Y. Tang, Atul Butte, Ervin Epstein, Kavita Y. Sarin, and Anthony E. Oro
NOTCH3 regulates stem-to–mural cell differentiation in infantile hemangioma
NOTCH3 is necessary for perivascular cell differentiation and infantile hemangioma development in mice.
Andrew K. Edwards, Kyle Glithero, Peter Grzesik, Alison A. Kitajewski, Naikhoba C.O. Munabi, Krista Hardy, Qian Kun Tan, Michael Schonning, Thaned Kangsamaksin, Jan K. Kitajewski, Carrie J. Shawber, and June K. Wu
Neutralization of IL-8 decreases tumor PMN-MDSCs and reduces mesenchymalization of claudin-low triple-negative breast cancer
A clinical-stage anti-IL8 antibody reduces the recruitment of PMN-MDSCs at the tumor site and decreases mesenchymal features in claudin-low triple negative breast cancer models.
Charli Dominguez, Kristen K. McCampbell, Justin M. David, and Claudia Palena
T cells presenting viral antigens or autoantigens induce cytotoxic T cell anergy
T cell antigen expression induces effector CTL anergy that protects T cells from autoimmune targeting but makes lymphotrophic viruses difficult to eradicate.
Nathalie E. Blachère, Dana E. Orange, Emily C. Gantman, Bianca D. Santomasso, Graeme C. Couture, Teresa Ramirez-Montagut, John Fak, Kevin J. O’Donovan, Zhong Ru, Salina Parveen, Mayu O. Frank, Michael J. Moore, and Robert B. Darnell
B cell–derived IL-4 acts on podocytes to induce proteinuria and foot process effacement
IL-4 is a B cell-derived cytokine capable of generating podocyte injury and proteinuria.
Alfred H.J. Kim, Jun-Jae Chung, Shreeram Akilesh, Ania Koziell, Sanjay Jain, Jeffrey B. Hodgin, Mark J. Miller, Thaddeus S. Stappenbeck, Jeffrey H. Miner, and Andrey S. Shaw
Loss of miR-141/200c ameliorates hepatic steatosis and inflammation by reprogramming multiple signaling pathways in NASH
Levels of miR-141 and miR-200c were elevated in livers of mice and humans with NASH, and deletion of miR-141/200c protected mice from developing NASH.
Melanie Tran, Sang-Min Lee, Dong-Ju Shin, and Li Wang
Maternal obesity and increased neonatal adiposity correspond with altered infant mesenchymal stem cell metabolism
Umbilical cord-derived mesenchymal stem cell-specific alterations in metabolism and gene expression correlate with maternal obesity and neonatal adiposity.
Peter R. Baker II, Zachary Patinkin, Allison L.B. Shapiro, Becky A. De La Houssaye, Michael Woontner, Kristen E. Boyle, Lauren Vanderlinden, Dana Dabelea, and Jacob E. Friedman
Microbiota control immune regulation in humanized mice
The microbiota controls immune regulation by affecting dendritic cells in the gut wall, and changes in the microbiome may reduce toleragenic mechanisms and lead to T cell activation.
Elke Gülden, Nalini K. Vudattu, Songyan Deng, Paula Preston-Hurlburt, Mark Mamula, James C. Reed, Sindhu Mohandas, Betsy C. Herold, Richard Torres, Silvio M. Vieira, Bentley Lim, Jose D. Herazo-Maya, Martin Kriegel, Andrew L. Goodman, Chris Cotsapas, and Kevan C. Herold
Notch1 haploinsufficiency causes ascending aortic aneurysms in mice
Notch1 heterozygous mice in a 129S6 background display ascending aortic dilation and haploinsufficiency in the second heart field lineage causes ascending aortic aneurysms.
Sara N. Koenig, Stephanie LaHaye, James D. Feller, Patrick Rowland, Kan N. Hor, Aaron J. Trask, Paul M.L. Janssen, Freddy Radtke, Brenda Lilly, and Vidu Garg
Macrophage-derived oncostatin M contributes to human and mouse neurogenic heterotopic ossifications
Macrophage-derived Oncostatin M contributes to the development of heterotopic ossification with hematopoietic niches following brain/spinal cord injuries in human and in a mouse model.
Frédéric Torossian, Bernadette Guerton, Adrienne Anginot, Kylie A. Alexander, Christophe Desterke, Sabrina Soave, Hsu-Wen Tseng, Nassim Arouche, Laetitia Boutin, Irina Kulina, Marjorie Salga, Beulah Jose, Allison R. Pettit, Denis Clay, Nathalie Rochet, Erica Vlachos, Guillaume Genet, Charlotte Debaud, Philippe Denormandie, François Genet, Natalie A. Sims, Sébastien Banzet, Jean-Pierre Levesque, Jean-Jacques Lataillade, and Marie-Caroline Le Bousse-Kerdilès
Genetic determinants of circulating GIP and GLP-1 concentrations
GWAS of circulating fasting and glucose-stimulated concentrations of incretins GIP and GLP-1 identifies new genetic loci involved in hormone secretion and metabolism
Peter Almgren, Andreas Lindqvist, Ulrika Krus, Liisa Hakaste, Emilia Ottosson-Laakso, Olof Asplund, Emily Sonestedt, Rashmi B. Prasad, Esa Laurila, Marju Orho-Melander, Olle Melander, Tiinamaija Tuomi, Jens Juul Holst, Peter M. Nilsson, Nils Wierup, Leif Groop, and Emma Ahlqvist
Secreted PLA2 group X orchestrates innate and adaptive immune responses to inhaled allergen
Secreted phospholipase A2 group X (sPLA2-X) plays a key role in controlling both innate and adaptive type-2 immune responses.
James D. Nolin, Ying Lai, Herbert Luke Ogden, Anne M. Manicone, Ryan C. Murphy, Dowon An, Charles W. Frevert, Farideh Ghomashchi, Gajendra S. Naika, Michael H. Gelb, Gail M. Gauvreau, Adrian M. Piliponsky, William A. Altemeier, and Teal S. Hallstrand
Human vaccination against RH5 induces neutralizing antimalarial antibodies that inhibit RH5 invasion complex interactions
A clinical trial of a vaccine targeting the blood-stage RH5 antigen from Plasmodium falciparum demonstrates it is safe and immunogenic, inducing functional strain-transcending antibodies.
Ruth O. Payne, Sarah E. Silk, Sean C. Elias, Kazutoyo Miura, Ababacar Diouf, Francis Galaway, Hans de Graaf, Nathan J. Brendish, Ian D. Poulton, Oliver J. Griffiths, Nick J. Edwards, Jing Jin, Geneviève M. Labbé, Daniel G.W. Alanine, Loredana Siani, Stefania Di Marco, Rachel Roberts, Nicky Green, Eleanor Berrie, Andrew S. Ishizuka, Carolyn M. Nielsen, Martino Bardelli, Frederica D. Partey, Michael F. Ofori, Lea Barfod, Juliana Wambua, Linda M. Murungi, Faith H. Osier, Sumi Biswas, James S. McCarthy, Angela M. Minassian, Rebecca Ashfield, Nicola K. Viebig, Fay L. Nugent, Alexander D. Douglas, Johan Vekemans, Gavin J. Wright, Saul N. Faust, Adrian V.S. Hill, Carole A. Long, Alison M. Lawrie, and Simon J. Draper
Collections of note
Nephrology: New insights on glomerular hyperfiltration: a Japanese autopsy study (Go Kanzaki ... Takashi Yokoo, John F. Bertram), Injury-induced actin cytoskeleton reorganization in podocytes revealed by super-resolution microscopy (Hani Y. Suleiman ... Andrey S. Shaw, Jeffrey H. Miner), 25+ more
Neuroscience: Increased putamen hypercapnic vasoreactivity in levodopa-induced dyskinesia (Vincent A. Jourdain ... Vijay Dhawan, David Eidelberg, Retinal amyloid pathology and proof-of-concept imaging trial in Alzheimer’s disease (Yosef Koronyo ... Keith L. Black, Maya Koronyo-Hamaoui), 35+ more
Cell biology

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