News & Views in 2002

Type 1 diabetes has long been thought of as a T cell–mediated disease. Now, a new study in mice makes a strong case that maternal autoantibodies can play an essential role in the initiation of diabetes. (pages 399–402)

Tumor cells engineered to overexpress molecules that activate an immune response have shown therapeutic promise in preventing growth of cancers. In a new study, tumor cells studded with a ligand-mimicking antibody fragment beckon their own destruction. (pages 343–348)

A small-molecular-weight drug originally developed to treat cancer produces sustained reduction in body weight in obese mice by a novel hypothalamic mechanism. The findings suggest new targets for the development of anti-obesity drugs.

A study suggesting that many genes, each conferring a small risk, account for most cases of breast cancer could have important implications for population-based prevention programs—provided that the genes can be identified.

The finding that CD39 on Langerhans cells modulates inflammation and immunity in the skin might lead to new strategies to alter immune responses to benefit patients and suggests a new in vitro technique for assessing the irritant potential of topical agents. (pages 358–365)

The finding that fetal mouse neural stem cells do not differentiate into hematopoietic cells contradicts findings from earlier reports and adds to the controversy regarding the rigor of the experimental methods used to demonstrate the differentiation repertoire of stem cells. (pages 268–273)

The finding that cloned mice, produced by transfer of nuclei from cumulus cells, develop obesity but do not transmit the phenotype to their offspring provides further evidence that cloned embryos are vulnerable to epigenetic change. (pages 262–267)

The leucine-rich repeat-containing gene, LGI1, was identified as a possible tumor suppressor gene involved in brain tumor development. It now appears that it also plays a role in abnormal brain development that leads to epilepsy.

The development of anticancer therapies that target apoptosis pathways may be hampered by resistance of certain tumor cells to death signals. New findings show that tumor cells lacking the pro-apoptotic protein Bax are resistant to apoptosis induced by the death ligand TRAIL, but that chemotherapeutic drugs can restore their sensitivity to TRAIL. (pages 274–281)

Interactions between recipient T cells and donor endothelial graft cells may be an important mechanism for both acute and chronic rejection of vascularized allografts. This finding provides a starting point for investigations to develop novel ways of inducing long-lasting immunologic tolerance to donor antigens. (pages 233–239)

Migraine sufferers experience pounding headaches, which sometimes are preceded by a visual aura. Now Bolay et al. show that cortical-spreading depression, the cause of the aura, activates trigeminal afferents, which act to cause inflammation of the pain-sensitive meninges, generating the headache. (pages 136–142)

The α isoform of the IκB protein kinase has been identified as the missing link in a signaling pathway that controls mammary epithelial proliferation via the cell-cycle regulator cyclin D1. This new player may provide a promising target for inhibiting cyclin D1 expression, which is elevated in 50% of breast malignancies.

Increased levels of circulating triglyceride and free fatty acids are common features of diabetic dyslipidemia. Positional cloning has led to the identification of a liver-derived protein, angiopoietin-like protein 3, that is largely responsible for diabetic dyslipidemia in an animal model of type 2 diabetes mellitus.

Mucosal cells are the principal portal of HIV-1 entry. A new study in this issue shows that upon contact with a X4 and R5 virus subtype mixture present in the inoculum, mucosal epithelial cells are themselves resistant to virus infection. Rather, they select the R5 virus subtype for transport across the cell, bringing the virus in contact with mucosal CD4⁺ T lymphocytes, which starts the chain of infection. (pages 150–156)

The demonstration that transplanted embryonic stem cells differentiate into functional dopamine neurons and provide stable functional recovery in a rodent model of Parkinson disease moves the field a step closer to clinical applications of embryonic stem cells.