News & Views in 2003

A frenzied bout of evolution occurs every flu season, as viruses test the limits of the human immune system. Variants that can evade attack by cytotoxic T cells gain a firm foothold in the viral population even if they confer an advantage in a low percentage of human hosts. A new mathematical model examines this unusual dynamic.

Amyotrophic lateral sclerosis has not responded well in clinical trials to what initially seemed a promising therapy—the administration of neuronal growth and survival factors. Now, a gene therapy-based approach in mice revives hope that proper delivery of such factors can slow the disease's course.

A polymorphism present in about half the general population can predispose to heart failure as well as enhance responsiveness to β-blockers. The mechanism for this is now being revealed (pages 1300–1305).

Viruses need cellular proteins to help them escape from cells. New results show that HIV and other viruses use the cellular machinery that normally delivers proteins to late endosomes and lysosomes.

During pregnancy, tryptophan degradation in the placenta protects a growing fetus from attack by T cells. Tumor cells are now shown to exploit this unusual system to prevent rejection by tumor-specific cytotoxic T cells (pages 1269–1274).

Robust regeneration of hair cells, which mediate hearing and balance in the ear, occurs in most vertebrates, with the exception of mammals. Now, the identification of stem cells in the mouse inner ear that can give rise to hair cells raises the prospect of inducing regeneration in mammals as well (pages 1293–1299).

Antibodies to the CD40 ligand have modulated the immune system in animal experiments and in human clinical trials. Assumptions about how these antibodies work are now reexamined (pages 1275–1280).

Bone marrow–derived stem cells have been used with some success in animal models to repair ischemic damage to the heart. Overexpression of the survival-promoting signal Akt greatly enhances the ability of these cells to heal a heart after myocardial infarction (pages 1195–1201).

An intestinal peptide that regulates glucose metabolism by stimulating insulin secretion from the pancreas is now shown to enhance learning and memory. The peptide can also protect nerve cells in models of neurodegenerative disorders (pages 1173–1179).

Since the eradication of natural smallpox infection, research efforts have waned and the vaccine is now outdated. Two studies revitalize efforts to create a new smallpox vaccine. One study moves vaccine production from animals into tissue culture; the other examines duration of immunity in already vaccinated individuals (pages 1125–1139 and 1131–1137).

Transplantation of bone marrow between allogeneic donors and recipients poses the risk of developing graft-versus-host disease, mediated by T cells from the graft. Exploitation of naturally occurring regulatory T cells in the graft minimizes this risk while still allowing another crucial function of graft T cells—the eradication of host tumor cells. (pages 1144–1150)

Neuropathic pain syndromes such as phantom limb pain have remained enigmatic to patients, physicians and researchers alike. A new study reveals how nerve damage may alter the pain threshold and lead to such syndromes.

Why are humans particularly susceptible to HIV-1, whereas our monkey cousins are impervious to the virus? Part of the answer may lie with the virus' interaction with a cellular system of defense (pages 1138–1143).

Bacterial signaling systems have come into vogue lately as mediators of successful interactions with the host. Now it appears that human hormones present in the gut interact with one such signaling system.

An approach that aims to correct RNA improves muscle function in a mouse model of a disease particularly recalcitrant to gene therapy: Duchenne muscular dystrophy (pages 1009–1014).

Cadmium is a toxic environmental pollutant that has worrisome estrogenic effects in cell culture. New data from rats show that cadmium can act as an estrogen mimic in the whole animal, inducing conditions ranging from uterine hyperplasia to early onset of puberty (pages 1081–1084).