Tracking malaria parasites in the liver
Plasmodium falciparum is the most deadly human malaria parasite, causing more than 800,000 deaths per year. After the parasite enters the blood stream, it travels to the liver where it serially invades liver cells (hepatocytes), until it settles down to form a parasitophorous vacuole (PV). Once ensconced in its PV, the parasite undergoes a process known as liver stage (LS) development during which it spawns tens of thousands of new parasites. In this issue of the Journal of Clinical Investigation, Stefan Kappe and colleagues at the Seattle Biomedical Research Institute report on a human liver-chimeric mouse that replicates P. falciparum LS development in humans. This is the first reliable model for the study of the P. falciparum LS stage and will be important for understanding human host/parasite interactions during the course of malaria infection.
TITLE:
Complete Plasmodium falciparum liver stage development in liver-chimeric mice
AUTHOR CONTACT:
Stefan Kappe
Seattle Biomedical Research Institute, Seattle, WA, USA
Phone: (206) 256-7205; E-mail: stefan.kappe@seattlebiomed.org
View this article at: http://www.jci.org/articles/view/62684?key=cc5ea46c50fc922c3f51
Researchers iron out the link between serum ferritin and diabetes
Iron overload increases the risk for insulin resistance and type 2 diabetes; however, the exact mechanisms that link the two are unknown. In this issue of the Journal of Clinical Investigation, Donald McClain and colleagues at the University of Utah report that serum ferritin levels could predict the presence or absence of metabolic syndrome in humans and were inversely associated with the expression of adiponectin, a blood glucose-regulating protein produced by fat cells (adipocytes). Treatment of adipocytes with iron decreased adiponectin levels, indicating that adipocytes play a central role in nutrient and iron detection. Further, reduction of serum ferritin levels in human patients increased insulin sensitivity and glucose tolerance. This study underscores the importance of adipocytes in metabolic diseases and points to iron reduction as a possible treatment for diabetes.
TITLE:
Adipocyte Iron Regulates Adiponectin and Insulin Sensitivity
AUTHOR CONTACT:
Don McClain
University of Utah, Salt Lake City, UT, USA
Phone: 801 585-0954; Fax: 801 585-0956; E-mail: donald.mcclain@hsc.utah.edu
View this article at: http://www.jci.org/articles/view/44421?key=5dbdc2ade3dc70280124
Influenza-infected lung cells send an SOS to the immune system
Influenza can cause viral pneumonia in humans, leading to lung failure. The virus damages the alveolar epithelial cells, which release molecular attractants to bring immune cells to the site of infection. Until recently, the identity of these immune attractants was unknown. In this issue of the Journal of Clinical Investigation, researchers led by Suzanne Herold at the University of Giessen report that alveolar cells produce granulocyte-colony stimulating factor (GM-CSF) to drive the accumulation of immune cells in a mouse model of influenza-associated pneumonia. GM-CSF protected mice against influenza infection, while loss of GM-SCF compromised their immune response and resulted in a more severe lung infection. These results suggest that GM-CSF is crucial for protection and recovery from influenza-mediated lung injury and has implications for treatment of influenza-associated pneumonia.
TITLE:
Alveolar epithelial cells orchestrate DC function in murine viral pneumonia
AUTHOR CONTACT:
Susanne Herold
UGLC, Giessen, UNK, DEU
Phone: 0049-641-985-42552; Fax: 0049-641-985-42568; E-mail: susanne.herold@innere.med.uni-giessen.de
View this article at: http://www.jci.org/articles/view/62139?key=725cc74433800775e7b8
Regulating long-term memory storage
Memories are initially stored in a fragile form. A process known as memory consolidation converts these short-term memories into stable long-term memories. Memory consolidation requires changes in gene expression, which are regulated by molecules known as nuclear receptors. In this issue of the Journal of Clinical Investigation, researchers led by Ted Abel at the University of Pennsylvania identified nuclear receptors that are important for memory formation in mice. In the hours after performing a memory-forming task, the mice had increased expression of the Nr4a nuclear receptor family. Blocking the activity of these receptors prevented long term memory formation without impacting short-term memory. Further, increased expression of Nr4a improved the effect of a memory-enhancing class of drugs known as histone-deacetylase inhibitors. This study demonstrates that the Nr4a receptor family contributes to memory formation and may serve as a therapeutic target for improving cognition.
TITLE:
NR4A nuclear receptors support memory enhancement by histone deacetylase inhibitors
AUTHOR CONTACT:
Ted Abel
University of Pennsylvania, Philadelphia, PA, USA
Phone: 215-746-1122; E-mail: abele@sas.upenn.edu
View this article at: http://www.jci.org/articles/view/64145?key=04aefa54c80df948c56b
Not so fast: PPARβ/δ slows insulin secretion
Type 2 diabetes is characterized by high plasma glucose levels, insulin resistance, and inadequate insulin production. Insulin is secreted by pancreatic β islets and the number of β islets strongly influences the body's ability to process glucose. In this issue of the Journal of Clinical Investigation, Walter Wahli and colleagues at the University of Lausanne report that PPARβ/δ, a protein that regulates gene expression, is a critical mediator of β islet insulin secretion in mice. PPARβ/δ-mutant mice had more β islets and enhanced insulin secretion compared to normal mice. By examining the genes that were expressed in normal and mutant β islets, Wahli and colleagues found that PPARβ/δ represses genes that help β islets secrete insulin. Further, islets lacking PPARβ/δ released insulin more quickly than normal islets, suggesting that therapeutics targeting PPARβ/δ in the pancreas may help stimulate insulin release in diabetic patients.
TITLE:
PPARβ/δ affects pancreatic β-cell mass and insulin secretion in mice
AUTHOR CONTACT:
Walter Wahli
Center for Integrative Genomics, National Research Center Frontiers in Gene, Lausanne, UNK, CHE
Phone: +41 21 692 41 10; Fax: +41 21 692 41 15; E-mail: walter.wahli@unil.ch
View this article at: http://www.jci.org/articles/view/42127?key=8d924abba94838e6f75c
MicroRNAs regulate insulin production
Obesity and pregnancy are associated with diminished insulin sensitivity, accompanied by an increase in the demand for insulin. To compensate the pancreas expands its population of insulin-producing β islet cells. Researchers led by Romano Regazzi at the University of Lausanne have identified a microRNA that participates in β islet expansion. In this issue of the Journal of Clinical Investigation, Regazzi and colleagues report that decreases in the microRNA miR-338-3p were correlated with increases in the number of β islets during pregnancy in rats. Blocking miR-338-3p increased β islet expansion, suggesting that regulation of this microRNA may be important in disease states associated with insulin resistance, such as gestational diabetes.
TITLE:
MicroRNAs contribute to compensatory beta-cell expansion during pregnancy and obesity
AUTHOR CONTACT:
Romano Regazzi
University of Lausanne, Lausanne, , CHE
Phone: 41216925280; Fax: 41216925255; E-mail: romano.regazzi@unil.ch
View this article at: http://www.jci.org/articles/view/64151?key=a785263ccfaf764e19bc
Complex genetic regulation underlies GATA2-linked human diseases
GATA2 is a master regulator of the formation and development of hematopoietic stem/progenitor cells (HSPCs), which form the various types of blood cells. Dysregulation of GATA2 has been linked to several different human disease states, including leukemia, and MonoMAC and Emberger syndromes. In this issue of the Journal of Clinical Investigation two research groups report on genetic regulatory elements that profoundly alter the expression and activity of GATA2. James Douglas Engel and colleagues at the University of Michigan disrupted GATA2 expression in the endothelial tissue of mice, which resulted in embryonic lethality that was attributed to the loss of liver HSPCs and defective lymphatic vasculature development. Researchers led by Emery Bresnick at the University of Wisconsin at Madison identified a new mutation in a GATA2 genetic regulatory element in a MonoMAC patient. Deletion of this regulatory element in mice caused embryonic lethality that was also linked to depletion of liver HSPCs and a loss of vascular integrity. Both of these studies underscore the role of GATA2 in vascular integrity and may help define the pathology of GATA2-associated human diseases.
TITLE:
Conditional GATA2 inactivation results in HSC loss and lymphatic mispatterning
AUTHOR CONTACT:
James Engel
The University of Michigan Medical Schoolool, Ann Arbor, MI, USA
Phone: 734-615-7509; Fax: 734-615-8500; E-mail: engel@umich.edu
View this article at: http://www.jci.org/articles/view/61619?key=d5e2c570893c08d9bdf8
ACCOMPANYING ARTICLE
TITLE:
Cis-element mutated in GATA2-dependent immunodeficiency governs hematopoiesis and vascular integrity
AUTHOR CONTACT:
Emery Bresnick
University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
Phone: 608-265-6446; E-mail: ehbresni@wisc.edu
View this article at: http://www.jci.org/articles/view/61623?key=b9cc4326e2fd3ad9ae8d
Journal
Journal of Clinical Investigation