Cholesterol gallstone disease occurs when cholesterol builds up in bile and precipitates in the gallbladder. Previous work suggested that the nuclear hormone receptor FXR (farnesoid X receptor) helps maintain normal bile acid metabolism. On page 1352 of this issue, Moschetta et al. show that mice lacking FXR have symptoms of cholesterol gallstone disease, and that a compound that activates FXR prevents gallstone formation. The cover image shows cholesterol monohydrate crystals from gallbladder bile of mice with cholesterol gallstone disease.

The cover depicts a colored transmission electron micrograph of replicating Ebola virus particles. The virus replicates inside the host's cells, forming a spindle from which new virus particles are released. Credit: London School of Hygiene & Tropical Medicine/Science Photo Library

The cover depicts a side view, three-dimensional, magnetic resonance imaging scan of the white matter pathways throughout the brain. The blue color represents neuronal pathways running from the top (cortex)to the bottom (brainstem) of the brain, green colors represent pathways running from the front (left side of image) to the back (right side of image), and red colors show pathways running between the right and left hemispheres of the brain. Images and Text Copyright © 2003 Tom Barrick, Chris Clark, SGHMS/Photo Researchers, Inc. All Rights Reserved.

Mutations affecting the forkhead transcription factor FoxC2 are known to underlie lymphedema-distichiasis syndrome. On page 974 of this issue, Petrova et al. show that FoxC2 is important for lymphatic valve morphogenesis and for keeping lymphatic capillaries free of pericytes. The cover image shows abnormally patterned and enlarged lymphatic vessels in the skin of Foxc2+/−; Vegfr3+/lacZ embryos (visualized by staining for β-galactosidase).

The cover shows purine P2X7 receptors (red) in spinal cord motor neurons (blue) stained for the neuronal antigen MAP-2 and counterstained with a nuclear marker (DAPI, dark blue/black). On page 821 of this issue, Wang et al. show that blocking these receptors after spinal cord injury improved functional recovery, supported neuronal survival and diminished cell death around the area of the lesion. Magnification, x100.

Bone marrow-derived cells can therapeutically fuse with hepatocytes in the fumarylacetoacetate hydrolase (Fah)-deficient mouse, a model of liver disease. On page 744 of this issue, Willenbring et al. show that myelomonocytic cells, including macrophages, are effective fusion partners for hepatocytes in vivo. The cover is a stylized depiction of a fused hepatocyte (stained orange for Fah) containing three nuclei stained for presence of the X chromosome (green) and host-derived Y chromosomes (pink). Total magnification, x1,500.

Oligodendrocyte precursor cells in primary culture, which were isolated from the spinal cord 3 days after contusion injury. Improving the ability of such endogenous cells to promote recovery by increasing cAMP levels (see paper by Pearse et al., page 610 may be a new therapeutic target for the treatment of spinal cord injury. Image courtesy of Soonmoon Yoo and Jean Wrathall.

Heart disease is the number one cause of death in the United States, and this month's installment of our 10th anniversary focus series homes in on cardiovascular disease. On page 467, Eric Olson casts the past decade's progress in cardiovascular research in historical perspective. Special news features, a historical News and Views and historical Research Notes round out our special content. Cover image depicts the human heart, courtesy of Getty images.

The protein Nogo is a well-known inhibitor of axonal outgrowth and repair in the nervous system. On page 382 of this issue, Acevedo et al. show that Nogo also acts in the vasculature, regulating remodeling in response to injury (see also the related News & Views on page 348). The cover image shows immunofluorescent staining of Nogo (red) in an uninjured femoral artery (phalloidin staining is in gree and DAPI staining in blue). Magnification, x63.

Severe acute respiratory syndrome (SAR) emerged last year as a threat to global health. On page 290 of this issue, Haagmans et al. show that pegylated interferon-alpha is an effective prophylactic in a macaque model of respiratory infection by SARS coronavirus. The cover image shows a transmission electron micrograph of SARS coronavirus nucleocapsids (purple) in a type 1 alveolar pneumocyte from the lung of an infected macaque. Magnification, approximately x50,000.

Physical barriers within tumor matrices can hinder deliverance of therapeutic agents to cancer cells, and make it difficult to measure macromolecule diffusion. In this month's Technical Report, Alexandrakis et al. (page 203) present a microscopy technique that reveals the intricate nature of barriers within tumors. The cover image shows GFP-marked glioblastoma cells (green) in the cranial window of a mouse visualized using two-photon fluorescence correlation microscopy. Tumor vessels are labeled with rhodamine-dextran (red), and collagen fibers are shown in purple. The image width is 250 µm.

In 2004, Nature Medicine enters its tenth year of publication, continuing our mission to serve the biomedical research community as the venue for top-flight primary research articles, news and perspectives. The cover image commemorates our anniversary year with a collage of covers spanning our publication history. (Graphic by Lewis Long)