Reviews & Analysis

The zebrafish has become a popular model organism to investigate many biological processes, in part owing to the combination of facile genetic manipulation and rapid, external embryonic development. The application of large-scale screening to identify chemical suppressors of a cancer-prone mutant highlights new technology for whole organism–based small-molecule discovery.

Development of small-molecule agonists against members of the tumor necrosis factor (TNF) receptor superfamily remains a considerable challenge. Presentation of ligand-derived peptides on a trimeric scaffold may point the way toward development of potent small-molecule agonists against this biologically important protein superfamily.

Sir2 is a key regulator in promoting longevity in response to a low-calorie diet. A new role for nitric oxide in promoting mitochondrial synthesis may be the reason why.

Identification of the monocarboxylate transporter 1 as a target of a new class of immunosuppressants shows that aerobic glycolysis and lactate release are essential for the proliferation of activated lymphocytes.

During the past century, the sea lamprey colonized the Great Lakes of North America and decimated the commercial fishing industry. The isolation and characterization of a migratory pheromone from the sea lamprey expands options for control of this invading species.

In the brain, neurotransmitter-receptor binding represents the moment of stereochemical recognition in which one neuron senses the signal sent by another. Submillisecond time-resolved FTIR spectroscopy now provides a first glimpse of the generative protein-ligand interactions that lead to glutamate receptor ion channel activation.

Cross-species quorum sensing in bacteria is mediated by a small molecule autoinducer, AI-2. It has now been demonstrated that AI-2–mediated signaling can be sabotaged by bacteria that degrade AI-2.

Kinesins are the molecular motors responsible for movement of vesicles inside cells. Evidence is now presented for how kinesin moves forward, as well as side to side.

Coelichelin is a new tetrapeptide siderophore from Streptomyces coelicolor originally discovered by gene sequence analysis. Surprisingly, this tetrapeptide is assembled by a trimodular nonribosomal peptide synthetase.

Unlike many site-specific recombinases that require accessory proteins, the Cre recombinase itself organizes a synaptic complex to initiate the recombination reaction. A new study suggests how Cre recombinase accomplishes this catalytic feat.

The high polyunsaturated fatty acid content of mammalian sperm cell membranes makes them vulnerable to damaging oxidation. A carbohydrate-antioxidant polymer has been developed that greatly increases antioxidant levels in sperm, counteracting any detrimental effects and improving sperm function.

Nitrite, a ubiquitous stable oxidation byproduct of nitric oxide (NO) metabolism, is now entering the pantheon of signaling biochemical molecules. Nitrite may have the unique properties of a blood and tissue NO reservoir activated by physiological and pathological hypoxia.

Cytochrome c release from the mitochondria is a critical component of the apoptotic cell-death program. Cytochrome c–catalyzed peroxidation of cardiolipin, a mitochondrial phospholipid, has now been shown to lessen the binding of cytochrome c to the mitochondrial inner membrane and facilitate permeabilization of the outer membrane. These results describe a new and earlier pro-apoptotic role for cytochrome c.

Blocking gene expression by interfering with translation of mRNA can be accomplished by means of antisense or short interfering RNA strategies, but more potent inhibitors would act by inhibiting transcription of genomic DNA. Two new studies show efficient inhibition of transcription using single-stranded peptide nucleic acid or double-stranded RNA targeted to the open complex formed at the transcription start site.

Examples abound in nature in which organisms adapt and optimize their fitness in a given environment. A new study demonstrates that a cellular cost-benefit analysis drives growth optimization over the course of evolution by attenuation of protein expression levels.

Voltage-gated ion channels respond to alterations in membrane potential and mediate action potential in neurons. A recent study provides new insights into the structure and gating of the Shaker potassium channel.

Iron-sulfur clusters and hemes are two iron-containing prosthetic groups involved in important physiological functions. Identification of the gene responsible for anemia in a mutant zebrafish has revealed an unexpected link between iron-sulfur cluster assembly and heme synthesis in red blood cells.