News & Views in 2000

A population of stem cells that are capable of differentiating into endothelial and smooth muscle cells has been identified, offering improved prospects for vascular tissue engineering.

Disruption of the gene encoding the cholesterol modifying enzyme ACAT2 in mice leads to a reduced capacity to absorb cholesterol and resistance to diet-induced hypercholesterolemia. This suggests that ACAT2 may be a good target for prevention of atherosclerosis. (pages 1341–1347)

Transgenic manipulation of intracellular signaling pathways may be an effective and highly-specific means of modifying cardiac conduction and slowing heart rate during atrial fibrillation. Is it time to consider gene therapy as an approach to managing atrial tachyarrhythmias? (pages 1395–1398)

Multiple models have been proposed for the mechanism by which mutant superoxide dismutase 1 induces motor neuron death and amyotrophic lateral sclerosis. A combination of cell biology and genetics may soon lead to an answer.

A DNA vaccine protects macaques against Ebola virus infection. Is a human vaccine finally on the way?

Statins reduce the expression of the class II major histocompatibility complex (MHCII) by arterial cells, leading to a decreased T-cell response. This indicates that statins may be useful in treating graft atherosclerosis and other chronic inflammatory conditions. (pages 1399–1402)

Hypoxia-inducible factor (HIF) is a key transcriptional regulator of the cellular response to hypoxia that is upregulated in many common cancers. Blockade of the pathway may provide a new opportunity for the development of cancer therapeutics (pages 1335-1340).

A long search for the mechanism by which BRCA1 regulates DNA damage-inducible genes leads to a novel zinc finger protein, ZBRK1.

Proteins carrying (CAG)_n repeat expansions are believed to cause neurological diseases such as Huntington Disease through their toxic gain-of-function. It may be, however, that loss of normal protein function can also contribute to pathogenesis.

The extraordinary plasticity of tissue stem cells, such as the ability of blood stem cells to differentiate into liver, would intrigue even the ancient alchemists. Recent discoveries also force us to rethink cell lineage relationships and expand the potential for cell-based therapies (pages 1229–1234).

Signature tagged mutagenesis of N. meningitidis has identified genes that are required for septicemic infection. However, these high-tech studies also raise questions about how to choose the isolates of pathogens that will yield the most useful information (pages 1269–1274).

Developing a modern vaccine that is able to duplicate the protective immunity observered after immunization with irradiated P. falciparum (Pf) sporozoites requires identification of antigenic Pf proteins. The identification of Pf Liver Stage Antigen-3 and its ability to protect chimpanzees against sporozoite challenge suggests we are headed in the right direction (pages 1258–1263).

Current therapies for Parkinson disease focus mainly on symptomatic relief, but gene therapy approaches may offer the prospect of halting or reversing the progress of the disease process itself. A recent study provides evidence that sustained delivery of glial cell line-derived neurotrophic factor to the nigrostriatal system provides neuroprotection and functional recovery in a primate model of Parkinson disease.

Constitutive activation of Notch signaling in hematopoietic cells establishes an immortalized hematopoietic stem cell population capable of developing into both myeloid and lymphoid lineages. This system will be useful in determining Notch-mediated mechanisms of hematopoietic differentiation (pages 1278–1281).

The exact mechanism by which exfoliative toxin A (ETA), producedby Staphylococcal aureus, causes epidermal blistering has been elusive.A combined knowledge of the pathogenesis of pemphigus, cell adhesion mechanisms,and the amino acid sequence of ETA led to a simple answer (pages 1275–1277).

We are finally beginning to unlock the mechanisms underlying Ca²⁺-stimulated muscle differentiation and cytokine-mediated muscle wasting. Gaining a better understanding of the signaling pathways that regulate muscle development and decay improves the prospects for repairing aged, injured and diseased muscle.