(Press-News.org) Cardiac conduction altered by intragenic enhancer
Genome-wide association studies (GWAS) have determined a surprising link between dysfunctional cardiac conduction and variants within SCN10A, which encodes nociceptor-associated sodium-gated ion channel subunit NaV1.8. Follow-up functional studies targeting NaV1.8 revealed only a minor contribution to cardiac physiology; therefore, it was unclear how SCN10A mutations promoted the development of cardiac conduction disease. In this issue of the Journal of Clinical Investigation, the research groups of Vincent Christoffels, Marcelo Nobrega, Phil Barnett, and Ivan Moskowitz teamed up and have now revealed that a transcriptional enhancer within SCN10A is required for cardiac expression of SCN5A, encoding the sodium-gated ion channel subunit NaV1.5, which is critical for cardiac conduction. In humans, a variant in the enhancer within SCN10A was associated with slowed conduction, Brugada syndrome, and reduced SCN5A transcription. In the accompanying Commentary, David Park and Glenn Fishman of the New York School of Medicine discuss how this study highlights the importance of functional studies to distinguish between coding and non-coding functions of genomic regions identified by GWAS.
TITLE:
A common genetic variant within SCN10A modulates cardiac SCN5A expression
AUTHOR CONTACT:
Ivan Moskowitz
The University of Chicago, Chicago, IL, USA
Phone: 773 834 0462; Fax: 773 834 2132; E-mail: imoskowitz@peds.bsd.uchicago.edu
View this article at: http://www.jci.org/articles/view/73140
ACCOMPANYING COMMENTARY
TITLE:
Nav-igating through a complex landscape: SCN10A and cardiac conduction
AUTHOR CONTACT:
Glenn I Fishman
NYU School of Medicine, New York, NY, USA
Phone: 212-263-3967; Fax: 212-263-3972; E-mail: glenn.fishman@med.nyu.edu
View this article at: http://www.jci.org/articles/view/75240
Inflammatory feedback loop promotes colorectal cancer metastasis
Induction of the epithelial-mesenchymal transition (EMT) in cancer cells is associated with an increased capacity to invade into surrounding tissue and migrate to distant sites. The tumor-specific factors that drive EMT aren't completely understood; however, evidence implicates inflammation in this process. In this issue of the Journal of Clinical Investigation, a team led by Heiko Hermeking at Ludwigs-Maximilians University determined that exposure of human colorectal cancer cells to the proinflammatory cytokine IL-6 activates the oncogenic transcription factor STAT3, which represses the gene encoding microRNA-34a (miR-34a) and promotes mesenchymal phenotypes. The IL-6 receptor (IL-6R) was identified as a direct target of miR-34a, defining an IL-6R/STAT3/miR-34a feedback loop that promotes EMT, invasion, and metastasis. Activation of p53, which induces miR-34a, decreased IL-6-dependent invasion and migration via reduced IL-6R expression, while loss of miR-34a in a murine model of colitis-associated cancer resulted in enhanced. In an accompanying Commentary, Raghu Kalluri and colleagues of the University of Texas MD Anderson Cancer Center discuss the role of tumor microenvironment in promoting EMT and metastasis.
TITLE:
IL-6R/STAT3/miR-34a feedback loop promotes EMT-mediated colorectal cancer invasion and metastasis
AUTHOR CONTACT:
Heiko Hermeking
Ludwigs-Maximilians University, Munich, , DEU
Phone: 011-49-89-2180-73685; Fax: 011-49-89-2180-73697; E-mail: Heiko.Hermeking@med.uni-muenchen.de
View this article at: http://www.jci.org/articles/view/73531
ACCOMPANYING COMMENTARY
TITLE:
Microenvironment-dependent cues trigger miRNA-regulated feedback loop to facilitate the EMT/MET switch
AUTHOR CONTACT:
Raghu Kalluri
University of Texas MD Anderson Cancer Center, Houston, TX, USA
Phone: 713-792-8586; E-mail: rkalluri@mdanderson.org
View this article at: http://www.jci.org/articles/view/75239?key=e516522eb60efe2d4b40
Insulin resistance in bone disrupts whole-body glucose homeostasis
Insulin signaling in osteoblasts mediates the activation of osteocalcin, which promotes insulin secretion in the pancreas and insulin sensitivity in other tissues. It is unknown if insulin resistance develops in bone in response to a high fat diet (HFD) and contributes to the disruption of glucose metabolism associated with the development of type 2 diabetes. In thie issue of the Journal of Clinical Investigation, Gerard Karsenty and colleagues of Columbia University determined that insulin resistance does develop in osteoblasts of mice fed a HFD and that this insulin resistance in bone cells contribute to the development of whole-body glucose intolerance through decreased circulation of active osteocalcin. Osteoblast-specific insulin resistance resulted, in part, from increased ubiquitination and degradation of the insulin receptor in response to saturated fatty acids. In the accompanying Commentary, Ryan Riddle and Thomas Clemens of Johns Hopkins University indicate that understanding the interplay between the skeletal system and whole-body metabolism will be beneficial for a wide range of metabolic diseases.
TITLE:
Bone-specific insulin resistance disrupts whole-body glucose homeostasis via decreased osteocalcin activation
AUTHOR CONTACT:
Gerard Karsenty
Columbia University, New York, NY, USA
Phone: 212 305 4011; E-mail: gk2172@columbia.edu
View this article at: http://www.jci.org/articles/view/72323
ACCOMPANYING COMMENTARY
TITLE:
Insulin, osteoblasts, and energy metabolism: why bone counts calories
AUTHOR CONTACT:
Thomas Clemens
Center for Musculoskeletal Research, John Hopkins, Baltimore, MD, USA
Phone: 410.955.3245; E-mail: tclemen5@jhmi.edu
View this article at: http://www.jci.org/articles/view/75554
Pathogenic interactions between platelets and neutrophils are mediated by AKT2
Pathological interactions between blood cells promote thrombo-inflammatory disease and result in complications such as vaso-occlusion during atherothrombosis, inflammation, and ischemia. Activated platelets, leukocytes and endothelial cells all contribute to the development of vaso-occlusion: though how interactions between these cell types are regulated is poorly understood. In this issue of the Journal of Clinical Investigation, Jaehyung Cho and colleagues at the University of Illinois determined that the serine/threonine kinase AKT2 was required for heterotypic aggregation of activated platelets, neutrophils and endothelial cells during TNF-α-induced vascular inflammation. In neutrophils, AKT2 phosphorylation activated and resulted in membrane translocation of αMβ2 integrin, which promoted cell-cell attachment. Neutrophils and platelets from patients with sickle cell disease (SCD) had increased levels of AKT phosphorylation, and specific inhibition of AKT2 diminished aggregation of these patients' cells. In SCD mice, targeting AKT2 reduced platelet-neutrophil aggregation and improved blood flow rates. In a companion Commentary, Gregory Vercellotti and John Belcher of the University of Minnesota discuss the complicated etiology of SCD-associated vaso-occlusion.
TITLE:
Neutrophil AKT2 regulates heterotypic cell-cell interactions during vascular inflammation
AUTHOR CONTACT:
Jaehyung Cho
University of Illinois at Chicago, Chicago, IL, USA
Phone: 312-355-5923; E-mail: thromres@uic.edu
View this article at: http://www.jci.org/articles/view/72305?key=ab5b2ca850b1530e92dd
ACCOMPANYING COMMENTARY
TITLE:
Not simply misshapen red cells: multimolecular and cellular events in sickle vaso-occlusion
AUTHOR CONTACT:
Gregory M Vercellotti
University of Minnesota, Minneapolis, MN, USA
Phone: 612 626 3757; Fax: 612 625 6919; E-mail: verce001@umn.edu
View this article at: http://www.jci.org/articles/view/75238
ALSO IN THIS ISSUE:
CLINICAL MEDICINE
TITLE:
Sympathetic activity–associated periodic repolarization dynamics predict mortality following myocardial infarction
AUTHOR CONTACT:
Axel Bauer
Eberhard Karls University, Tübingen, Tübingen, , DEU
Phone: + 49.7071.29.82922; E-mail: bauer@thebiosignals.org
View this article at: http://www.jci.org/articles/view/70085
STEM CELLS
TITLE:
Human muscle–derived stem/progenitor cells promote functional murine peripheral nerve regeneration
AUTHOR CONTACT:
Johnny Huard
University of Pittsburgh, Pittsburgh, PA, USA
Phone: 412-648-2798; Fax: 412-648-4066; E-mail: jhuard@pitt.edu
View this article at: http://www.jci.org/articles/view/44071
ONCOLOGY
TITLE:
Tumor endothelial marker 1–specific DNA vaccination targets tumor vasculature
AUTHOR CONTACT:
Andrea Facciabene
Ovarian Cancer Research Center, Philadelphya, PA, USA
Phone: 215-746-7071; Fax: 2155735129; E-mail: facciabe@mail.med.upenn.edu
View this article at: http://www.jci.org/articles/view/67382
NEPHROLOGY
TITLE:
Podocyte-specific RAP1GAP expression contributes to focal segmental glomerulosclerosis–associated glomerular injury
AUTHOR CONTACT:
Lewis Kaufman
Mount Sinai School of Medicine, New York, NY, USA
Phone: 646 245-2294; Fax: 212 987-0389; E-mail: lewis.kaufman@mssm.edu
View this article at: http://www.jci.org/articles/view/67846
INFORMATION:
JCI online ahead of print table of contents for March 18, 2014
2014-03-18
ELSE PRESS RELEASES FROM THIS DATE:
New from Geology: Fossils, earthquakes, gold, and sea-bed landslides
2014-03-18
Boulder, Colo., USA – Geology papers published 17 Mar. 2014 cover (1) modeling of seabed turbidity currents; (2) a large earthquake at Lake Vättern, Switzerland, about 11,500 years ago; (3) genesis of high-grade gold at the Porgera gold deposit, Papua New Guinea; (4) discovery of the Ediacaran guide fossil Cloudina sp. and the depositional age of the Bambuí Group; (5) earthquakes along the fossil Moho in Alpine Corsica; and (6) using LiDAR to better understand New Zealand's Alpine Fault.
Highlights are provided below. Geology articles published ahead of print can be accessed ...
NASA releases first interactive mosaic of lunar north pole
2014-03-18
Scientists, using cameras aboard NASA's Lunar Reconnaissance Orbiter (LRO), have created the largest high resolution mosaic of our moon's north polar region. The six-and-a-half feet (two-meters)-per-pixel images cover an area equal to more than one-quarter of the United States.
Web viewers can zoom in and out, and pan around an area. Constructed from 10,581 pictures, the mosaic provides enough detail to see textures and subtle shading of the lunar terrain. Consistent lighting throughout the images makes it easy to compare different regions.
"This unique image is a tremendous ...
Fierce 2012 magnetic storm barely missed Earth
2014-03-18
Earth dodged a huge magnetic bullet from the sun on July 23, 2012.
According to University of California, Berkeley, and Chinese researchers, a rapid succession of coronal mass ejections – the most intense eruptions on the sun – sent a pulse of magnetized plasma barreling into space and through Earth's orbit. Had the eruption come nine days earlier, it would have hit Earth, potentially wreaking havoc with the electrical grid, disabling satellites and GPS, and disrupting our increasingly electronic lives.
The solar bursts would have enveloped Earth in magnetic fireworks ...
New statistical models could lead to better predictions of ocean patterns
2014-03-18
COLUMBIA, Mo. – The world's oceans cover more than 72 percent of the earth's surface, impact a major part of the carbon cycle, and contribute to variability in global climate and weather patterns. However, accurately predicting the condition of the ocean is limited by current methods. Now, researchers at the University of Missouri have applied complex statistical models to increase the accuracy of ocean forecasting that can influence the ways in which forecasters predict long-range events such as El Nińo and the lower levels of the ocean food chain—one of the world's ...
Early detection of childhood eye cancer doesn't always improve survival, prevent eye loss
2014-03-18
For the most common form of childhood eye cancer, unilateral retinoblastoma, shortening the time from the first appearance of symptoms to diagnosis of disease has no bearing on survival or stage of the disease, according to a study by researchers at Columbia University Mailman School of Public Health in partnership with the Hospital Infantil de Mexico. The results appear online in the journal Cancer Epidemiology, Biomarkers & Prevention.
Because retinoblastoma is easily detectable by shining a light into a child's eye—often as a "cat's eye" reflection revealed through ...
The precise reason for the health benefits of dark chocolate: Mystery solved
2014-03-18
DALLAS, March 19, 2014 — The health benefits of eating dark chocolate have been extolled for centuries, but the exact reason has remained a mystery –– until now. Researchers reported here today that certain bacteria in the stomach gobble the chocolate and ferment it into anti-inflammatory compounds that are good for the heart.
Their findings were unveiled at the 247th National Meeting & Exposition of the American Chemical Society (ACS), the world's largest scientific society. The meeting, attended by thousands of scientists, features more than 10,000 reports on new advances ...
Building heart tissue that beats
2014-03-18
DALLAS, March 18, 2014 — When a heart gets damaged, such as during a major heart attack, there's no easy fix. But scientists working on a way to repair the vital organ have now engineered tissue that closely mimics natural heart muscle that beats, not only in a lab dish but also when implanted into animals. They presented their latest results at the 247th National Meeting & Exposition of the American Chemical Society (ACS), the world's largest scientific society.
The talk was one of more than 10,000 being presented at the meeting, which continues here through Thursday.
"Repairing ...
Bees capable of learning feats with tasty prize in sight
2014-03-18
They may have tiny brains, but bumblebees are capable of some remarkable learning feats, especially when they might get a tasty reward, according to two studies by University of Guelph researchers.
PhD student Hamida Mirwan and Prof. Peter Kevan, School of Environmental Sciences, are studying bees' ability to learn by themselves and from each other.
In the first study, published in February in Animal Cognition, the researchers found bees capable of learning to solve increasingly complex problems.
The researchers presented bees with a series of artificial flowers that ...
Sauder research shows why innovation takes a nosedive
2014-03-18
A new UBC study reveals that corporate leaders are victims of herd mentality when adopting new innovations, sometimes with deadly consequences.
The paper, by Sauder School of Business Associate Professor Marc-David L. Seidel and INSEAD Professor Henrich R. Greve, shows leaders tend to pursue innovations, even as complex as airplanes, based on early adoption by competitors not close scrutiny of the technical merits.
"Business leaders tend to panic when new innovations are about to hit the market. They scramble to buy an apparent early leader," says Seidel. "Sometimes ...
Stanford researchers survey protein family that helps the brain form synapses
2014-03-18
Neuroscientists and bioengineers at Stanford are working together to solve a mystery: how does nature construct the different types of synapses that connect neurons -- the brain cells that monitor nerve impulses, control muscles and form thoughts.
In a paper published in the Proceedings of the National Academy of Sciences, Thomas C. Südhof, M.D., a professor of molecular and cellular physiology, and Stephen R. Quake, a professor of bioengineering, describe the diversity of the neurexin family of proteins.
Neurexins help to create the synapses that connect neurons. Think ...