Volume 9

  • No. 12 December 2003

    Insulin resistance, a central feature of type 2 diabetes, is treated clinically by thiazolidinediones (TZDs), which are agonists of PPAR-gamma, a transcription factor expressed in insulin target tissues. On page 1491 of this issue, Hevener et al. show that loss of PPAR-gamma specifically in skeletal muscle results in insulin resistance and insensitivity to TZDs. This work offers insight into TZD action as well as mechanisms of fuel partitioning. The cover image depicts a partial structure of the insulin ß-chain. Courtesy of A. Pasieka/Photo Researchers Inc.

  • No. 11 November 2003

    Directing immune responses to kill tumor cells - by induction of apoptosis, for example - is a major goal of cancer immunotherapy. In this issue, Padua et al. (page 1413) present a vaccine strategy for treating promyelocytic leukemia, and Rubio et al. (page 1377) demonstrate a new method for detecting vaccine-induced tumorcytolytic T cells. The cover image shows a healthy human myeloid cell (upper cell) and a myeloid cell undergoing apoptosis (lower cell). Magnification, x11,000. Courtesy of Gopal Murti/Photo Researchers Inc.

  • No. 10 October 2003

    Inner ear stem cells triple-stained for the hair cell markers espin (beige) and F-actin (purple) and for pan-cytokeratin (orange), which labels inner ear supporting cells. On page 1293 of this issue, Li et al. identified cells from adult utricular sensory epithelium that have the capacity for self-renewal and are pluripotent, characteristic of stem cells. Shown are hair cell-like cells situated between larger cells expressing the supporting cell marker pan-cytokeratin. Differentiation of these stem cells into hair cell-like cells may impact future development of new therapies for the treatment of deafness.

  • No. 9 September 2003

    Heart ventricular sections of controls and rats injected with Akt-transduced stem cells. Mangi et al. genetically engineered rat mesenchymal stem cells, using ex vivo retroviral transduction, to overexpress the prosurvival factor Akt to the ischemic rat myocardium (page 1195). The authors were able to regenerate lost myocardial volume and normalize systolic and diastolic cardiac function. Sections are at the level of papillary muscle and are stained with Masson trichrome for collagen (blue) and viable muscle (red). Controls underwent coronary ligation and saline-only injection.

  • No. 8 August 2003

    Endothelin-1 (ET-1) mediates pain states ranging from trauma to cancer. On page 1055 of this issue, Khodorova et al. map a new peripheral analgesic pathway involving ET-1. In this pathway, ET-1 is released locally by keratinocytes after cutaneous injury, and triggers pain through endothelin-A receptors of local nociceptors. ET-1 also coincidentally produces analgesia by activating endothelin-B receptors (ET-B) on keratinocytes, inducing them to secrete β-endorphin, which in turn binds to the local nociceptors. The cover depicts a confocal image of rat epidermis, localizing ET-B (orange) on the surface and β-endorphin (green) in the cytoplasm of keratinocytes in the upper epidermal layers. (Magnification, x20.)

  • No. 7 July 2003

    The cover image represents 20 years of HIV science. The electron micrograph is one of the very first of HIV-1 particles, taken 4 February 1983, and the transition to the artist's rendition of an HIV particle as we understand it today represents our progress in knowledge. Depicted on the virion surface are the glycosylated envelope trimer and various cellular proteins. Inside the capsid are the two RNA molecules with nucleocapsid attached, plus reverse transcriptase, protease, Vpr and integrase. Vif is shown between the capsid and matrix layers.(Electron micrograph courtesy of the Institut Pasteur. Magnification x100,000. Graphic by Ken Eward of BioGrafx.)

  • No. 6 June 2003

    Advances in angiogenesis are leading to new therapies for ischemic injury and new approaches to treat cancer, blindness and other pathological disorders. On pages 653-725 of this issue, we present eight reviews in a special focus featuring the latest developments in angiogenesis research and its clinical applications. The reviews, and additional editorial content, are free to registered users on our website until 31 July 2003. The cover image depicts a stylized electron micrograph of vessels in the normal rat microvasculature.

  • No. 5 May 2003

    Ancient scourges have plagued humankind for centuries. There remains an urgent need to improve the efficacy of the live tuberculosis vaccine, Mycobacterium bovis BCG (bacillus Calmette-Guérin). Pym et al. reintroduced into the BCG strain genes encoding proteins that induce potent Th1 responses and subsequently better protect against virulent M. tuberculosis challenge (page 533). The cover image is a stylized electron micrograph of a macrophage engulfing M. tuberculosis bacteria. Magnification, ×2,000. On page 525, Krutzik et al. describe the regulation of Toll-like receptors in another ancient human scourge, leprosy.

  • No. 4 April 2003

    Neurogenesis in the adult brain has been an active topic of recent research. On page 439, Nunes et al. show that the subcortical white matter of the adult human brain harbors multipotential neural progenitor cells. These cells, selected with the A2B5 marker, are known to give rise to oligodendrocytes, but the new work suggests that multiple fates can be elicited under defined culture conditions. The cover depicts a white-matter progenitor-derived neurosphere giving rise in culture to multiple cell types, including ßIII-tubulin+ neurons (red), GFAP+ astrocytes (blue) and O4+ oligodendrocytes (green). Original magnification, x200.

  • No. 3 March 2003

    Harnessing the immune system to combat disease is the central tenet of immunotherapy. In this issue, two articles and a review discuss the effects of manipulating immune effector cells on the outcome of disease. On page 269 of this issue, Waldmann traces the history of immunotherapy, and on page 279, Brentjens and colleagues target ãƒâƒã‚âƒãƒâ‚ã‚âƒãƒâƒã‚â‚ãƒâ‚ã‚âŸ-cell tumors using genetically modified T cells. Finally, Yan et al. (page 287) demonstrate that blocking the cell surface marker RAGE suppresses experimental autoimmune encephalomyelitis induced by T cells. The cover image presents a stylized scanning electron micrograph of a large cancer cell surrounded by three cytotoxic T cells.

  • No. 2 February 2003

    The autoimmune disease type 1 diabetes hinges upon destruction of the insulin-producing β-cells of the pancreas. On page 198, Winer et al. show that the peri-islet Schwann cells, elements of the nervous system, are targets of auto-reactive T- and B-cell responses early in disease in the non-obese diabetic (NOD) mouse model. Represented on the cover are various stages of NOD pancreatic islet destruction (left, intact; bottom right, peri-insulitis; top, collapsed or destroyed). These include insulin-positive β-cells (red); Schwann cells positive for glial fibrillary acidic protein (blue); and CD3+ T cells (green). Magnification is x400-800.

  • No. 1 January 2003

    This month's issue highlights emerging trends in biomedical technology as a special focus of our New Technology section. On pages 97–145 we present reviews and commentaries on the latest advances in platform-based technologies, biomedical engineering and molecular imaging techniques. Online access to the content and a list of related articles will be available free to all users until 31 March 2003 at http://www.nature.com/nm/special_focus/new_tech/index.html. The cover image depicts an artist's rendition of the insight gained by the advent of the microarray.