Clues to flattened faces
Mutations in the Jagged1 gene cause Alagille syndrome, an inherited disorder that affects the liver, heart, kidneys and facial structure. Patients with Alagille syndrome often have a prominent forehead, a flattened midface and a prominent chin; some have a cleft palate.
To investigate how mutations in Jagged1 cause facial anomalies, Steven Goudy, M.D., and colleagues deleted the Jagged1 gene in mouse cranial neural crest cells – the main cell type that contributes to craniofacial development. They found that these mice had midfacial hypoplasia (incomplete development) similar to patients with Alagille syndrome. The studies point to a requirement for Jagged1 signaling at a specific time during midface and palate formation, for proper cellular division and extracellular matrix production. The researchers also found reduced branching of blood vessels, which could explain why some patients with Alagille syndrome are at risk of cerebral vascular bleeding.
The findings, reported in Human Molecular Genetics, suggest that Jagged1 acts on cranial neural crest cells both directly and indirectly to form the middle of the face.
This research was supported by the National Institute of Dental and Craniofacial Research, the National Heart, Lung and Blood Institute, and the National Institute of Diabetes and Digestive and Kidney Diseases.
— Leigh MacMillan
Meds’ benefits differ in dialysis patients
About half of kidney patients will die from heart disease within five years of starting dialysis, yet patients with kidney failure are rarely included in heart disease research.
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Jorge Gamboa, M.D., T. Alp Ikizler, M.D., and Nancy Brown, M.D., completed a small study that suggests a more personalized approach to selecting medication for heart disease prevention should be explored as a way to protect kidney failure patients from death from heart disease.
The article in the Journal of the American Society Nephrology compared angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). Both are prescribed to treat hypertension and reduce the risk of death, but Gamboa and his colleagues found each could have different effects on dialysis patients’ heart health. ARBs were found to be more effective at fighting inflammation while ACE inhibitors were better at preventing blood vessel damage.
This research was supported by grants from the National Heart, Lung and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Center for Research Resources, and the National Institute for General Medical Sciences.
— Carole Bartoo
Fishing for heart attack repair tools
Managing myocardial infarction – and the resulting heart failure – remains a clinical challenge. To search for chemicals that can stimulate cardiac muscle cell production, Vanderbilt Institute of Chemical Biology investigators led by Tao Zhong, Ph.D., Terri Ni, Ph.D., and Eric Rellinger, M.D., turned to a novel drug discovery tool: zebrafish.
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The researchers visually screened a library of chemical compounds foreffects on heart size in developing zebrafish embryos using fluorescence microscopy. They report in the journal Chemistry & Biology the identification of three related compounds named Cardionogen-1, -2 and -3 that selectively enlarged embryonic hearts by expanding the number of cardiac progenitor cells. They showed that these compounds promote the differentiation of mouse embryonic stem cells into cardiac muscle cells and that they inhibit the Wnt signaling pathway in mouse cells and zebrafish embryos.
The findings demonstrate the value of an in vivo zebrafish screen for revealing compounds that stimulate cardiac muscle cell production and may lead to novel therapeutic approaches for cardiac regeneration and repair.
This research was supported by the National Institute of Neurological Disorders and Stroke, the National Heart, Lung and Blood Institute, and the National Center for Research Resources.
— Leigh MacMillan
Green tea totals colorectal cancer
Tea and its phytochemical constituents have demonstrated anti-cancer properties in cell and animal experiments – particularly green tea, which has higher levels of antioxidant polyphenols than other types of tea.
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Gong Yang, M.D., MPH, and colleagues evaluated the association between green tea consumption and colorectal cancer risk in participants of the Shanghai Men’s Health Study. Among the 60,567 men in the study (aged 40 to 74), 243 developed colorectal cancer during the 5-year follow-up period.
They found that nonsmokers who drank green tea regularly had a 46 percent lower risk of colorectal cancer; however, no significant association was observed in smokers. Each 2-gram increment (approximately equivalent to the amount of tea in a tea bag) was associated with a 12 percent reduction in risk. The results, published in the November issue of Carcinogenesis, suggest that regular consumption of green tea may reduce risk of colorectal cancer among nonsmokers.
This research was supported by grants from the National Cancer Institute.
— Melissa Marino
We welcome suggestions for research to highlight in Aliquots. The items should be primary research articles (no reviews, editorials or commentaries) published within the last two months in a peer-reviewed journal. Please send the article citation (PDF if available) and any other feedback about the column to: aliquots@vanderbilt.edu.
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