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JCI early table of contents for May 8, 2013

Gene replacement in pigs ameliorates cystic fibrosis-associated intestinal obstruction

Cystic fibrosis (CF) is caused by mutations in CFTR and is characterized by dysfunction of the lungs, liver, pancreas, and intestines. Approximately 15% of babies with CF are born with an obstruction of the small intestine known as meconium ileus, frequently the first sign of CF. Unlike in humans, meconium ileus occurs in 100% of newborn CF pigs. In this issue of the Journal of Clinical Investigation, Michael Welsh and colleagues at the University of Iowa demonstrate that transgenic expression of normal CFTR in the intestine of CF pigs alleviated meconium ileus. Over time, the pigs still exhibited other manifestations of CF, including liver and lung disease, reduced weight gain, and pancreatic destruction. These findings provide insight into the pathophysiology of CF and indicate that tissue-specific, partial gene replacement can ameliorate intestinal symptoms of CF.

Intestinal CFTR expression alleviates meconium ileus in cystic fibrosis pigs

Michael Welsh
Howard Hughes Medical Institute, Iowa City, IA, USA
Phone: 319-335-7619; Fax: 319-335-7623; E-mail:

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Alzheimer's disease is associated with removal of the synaptic protein ADAM10

Alzheimer's disease is characterized by the accumulation of neurotoxic β-amyloid peptide (Aβ). ADAM10, a protein that resides in the neural synapses, has previously been shown to prevent the formation of Aβ. In this issue of the Journal of Clinical Investigation, Monica Di Luca and colleagues at the University of Milan in Milan, Italy, report that ADAM10 is removed from synapses through association with the protein AP2. Strikingly, the association between ADAM10 and AP2 was increased in human brain homogenates from Alzheimer's disease (AD) patients compared to healthy controls. Neuronal activity was shown to influence the level and activity of ADAM10 in synapses and its association with AP2. These studies identify pathological mechanisms associated with AD that control the localization of proteins at the synapse.

Endocytosis of synaptic ADAM10 in neuronal plasticity and Alzheimer's disease

Monica Di Luca
Universit degli Studi di Milano, Milano, ITA
Phone: +39-02-50318374; E-mail:

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BMPR2 is required for postimplantation uterine function and pregnancy maintenance

Martin Matzuk
Baylor College of Medicine, Houston, TX, USA
Phone: +1-713-798-6451; Fax: +1-713-798-5838; E-mail:

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CXCR4 downregulation of let-7a drives chemo-resistance in acute myeloid leukemia

Michael Andreeff
The Univ of Texas M.D. Anderson Cancer Center, Houston, TX, USA
Phone: 713-792-7260; Fax: 713-794-1903; E-mail:

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Endothelin-2 deficiency causes growth retardation, hypothermia, and emphysema in mice

Masashi Yanagisawa
The University of Texas Southwestern Medical Center, Dallas, TX, USA
Phone: 214-648-5082; Fax: 214-648-5068; E-mail:

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Apolipoproteins E and AV mediate lipoprotein clearance by hepatic proteoglycans

Jeffrey Esko
University of California, San Diego, La Jolla, CA, USA
Phone: 858 822-1100; Fax: 858 534-5611; E-mail:

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Nuclear receptor-microRNA circuitry links muscle fiber type to energy metabolism

Daniel P. Kelly
Sanford-Burnham Med Res Institute, Orlando, FL, USA
Phone: 407-745-2069; Fax: 407-745-2001; E-mail:

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Acylglycerol kinase augments JAK2-STAT3 signaling in esophageal squamous cells

Libing Song
Cancer Center, Sun Yat-sen University, Guangzhou, , CHN
Phone: +86(20)87335822; E-mail:

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Contact: Jillian Hurst
Journal of Clinical Investigation

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