Nature view

Research highlights from the NPG family of journals.

Cell-swapping transcription factors

Textbooks would have us believe that transcription factors have only cell-autonomous functions. But recent data suggest that some transcription factors (in particular, homeoproteins) move from cell to cell — raising the intriguing possibility that these proteins may be true signalling molecules. If so, how is this signalling regulated and what processes might it control? In this month's Nature Reviews Molecular Cell Biology, Alain Prochiantz and Alain Joliot review the latest evidence supporting this mode of signal transduction, and consider the possible functions of 'cell-switching' homeoproteins.

perspectives
Can transcription factors function as cell–cell signalling molecules?
A. PROCHIANTZ AND A. JOLIOT
Nature Reviews Molecular Cell Biology 4, 814; October 2003
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Putting the brakes on HIV-1 transmission

Heterosexual transmission accounts for 80% of the 40 million individuals infected with the HIV-1 virus. But only now — more than 20 years into the epidemic — are the events linking exposure to the virus and the establishment of infection becoming clear. In this month's Nature Reviews Microbiology, Robin Shattock and John Moore investigate how an improved understanding of the target cells involved, and how the virus attaches to these cells, is shaping new intervention strategies, based on the application of microbicides. These are agents designed to block the sexual transmission of HIV-1, and range from simple lubricants that reduce trauma to the mucosal epithelium, to specific inhibitors of HIV-1 attachment and fusion.

reviews
Inhibiting sexual transmission of HIV-1 infection
R. J. SHATTOCK AND J. P. MOORE
Nature Reviews Microbiology 1, 25; October 2003
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Up to 15% of patients in Western industrialized countries are affected by stress-related disorders. But before a study in this month's issue of Nature Neuroscience, we had little understanding about which detrimental effects of stress are mediated by brain circuits, and which by hormonal pathways. By using a genetically modified mouse line, Marianne Müller et al. were able to disentangle these two influences. They show that both specific forebrain neural circuits and the more general hypothalamic pituitary axis contribute to the normal adaptive responses to environmental challenges, and the pathology that results from chronic arousal of stress-emergency systems. Emeran Mayer and Michael Fanselow provide context in an accompanying News and Views article.

articles
Limbic corticotrophin-releasing hormone receptor 1 mediates anxiety-related behavior and hormonal adaptation to stress
M. B. MÜLLER et al.
Nature Neuroscience 6, 1100; October 2003
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new and views
Dissecting the components of the central response to stress
E. A. MAYER AND M. S. FANSELOW
Nature Neuroscience 6, 1011; October 2003
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Y chromosome held in the balance

A byproduct of homologous recombination between long Y-specific repeats in the human Y chromosome is the generation of deletions, some of which result in spermatogenic failure. In November's issue of Nature Genetics, Sjoerd Repping et al. report a 1.6-megabase deletion called gr/gr that is sufficiently common to be classed as a polymorphism. They have established that this deletion is a significant risk factor for spermatogenic failure — so why does it persist? The distribution of gr/gr-deleted chromosomes across the branches of the Y chromosome's genealogical tree suggests that the gr/gr deletion reflects a balance between natural selection and new mutation — homologous recombination continues to generate new deletions, whereas haploid selection culls gr/gr-deleted chromosomes from the population.

letters
Polymorphism for a 1.6-Mb deletion of the human Y chromosome persists through balance between recurrent mutation and haploid selection
S. REPPING et al.
Nature Genetics, 35, 247; October 2003
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Almonds vs. Carbohydrates in Weight Reduction

A low calorie diet supplemented with almonds, in contrast to complex carbohydrates, is associated with a greater increase in weight loss.

In this month's International Journal of Obesity, Wien et al. report on a 24 week trial of 65 overweight and obese adults to study the effect of an almond or complex carbohydrate enriched low calorie diet. Their results suggest that a low calorie diet supplemented with almonds is associated with greater reductions in weight/BMI, waist circumference, fat mass and systolic blood pressure

Papers
Almonds vs complex carbohydrates in a weight reduction program
M A WIEN, J M SABATÉ, D N IKLÉ, S E COLE & F R KANDEEL
International Journal of Obesity (2003) 27, 1365-1372.
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Drug Resistance: molecules and mechanisms

The identification and elucidation of cellular resistance mechanisms holds the promise of leading to better treatment for cancer patients. Guest edited by Gary D. Kruh, the current Oncogene Reviews issue contains 21 reviews by experts in the field of drug resistance that explore the molecules and mechanisms that attenuate the effects of anticancer agents. The agents covered range from retinoids, antiestrogens and Taxol to rituxamib and STI571. Included in the issue are concise reviews on apoptosis, DNA mismatch repair, p53, strategies for reversing drug resistance, transcriptional regulation of drug transporters and pharmacogenetics associated with drug methylation.

special
Oncogene Reviews: Drug resistance
Oncogene 22, (47)