Regulation of circadian rhythmicity

Daily rhythms in many behavioral, physiological, and biochemical functions are generated by endogenous oscillators that function as internal 24-hour clocks. Under natural conditions, these oscillators are synchronized to the daily environmental cycle of light and darkness. Recent advances in locating circadian pacemakers in the brain and in establishing model systems promise to shed light on the cellular and biochemical mechanisms involved in the generation and regulation of circadian rhythms.     

Deleted HTLV-I provirus in blood and cutaneous lesions of patients with mycosis fungoides.

Mycosis fungoides, a rare form of cutaneous T cell leukemia/lymphoma, is suspected of having a viral etiology on the basis of certain similarities to adult T cell leukemia, which is associated with human T cell leukemia/lymphoma virus type I (HTLV-I) infection. Cell lines were established from peripheral blood mononuclear cells (PBMC) of an HTLV-I-seronegative patient with mycosis fungoides. DNA hybridization analysis revealed the presence of HTLV-I-related sequences with unusual restriction endonuclease sites. Sequence analysis of subcloned fragments demonstrated the presence of a monoclonally integrated provirus with a 5.5-kilobase deletion involving large regions of gag and env and all of pol. Additional evidence for the presence of deleted proviruses was found by polymerase chain reaction (PCR) amplification of DNA from cutaneous lesions of five other HTLV-I-seronegative patients. The findings suggest that HTLV-I infection may be involved in the etiology of at least certain cases of mycosis fungoides.     

Cell cycle. Replication meets cohesion.

When a cell replicates its DNA during S phase of the cell cycle, the sister chromatid pairs must stick together like glue until they are separated to opposite ends of the cell (and hence into separate daughter cells) at anaphase. How the cell achieves this is still unclear but, as Takahashi and Yanagida explain in their Perspective, new findings in yeast have identified one molecule, Trf4p, that may be involved both in DNA replication and sister chromatid cohesion (Wang et al.).     

Vesicle endocytosis requires dynamin-dependent GTP hydrolysis at a fast CNS synapse

Molecular dependence of vesicular endocytosis was investigated with capacitance measurements at the calyx of Held terminal in brainstem slices. Intraterminal loading of botulinum toxin E revealed that the rapid capacitance transient implicated as "kiss-and-run" was unrelated to transmitter release. The release-related capacitance change decayed with an endocytotic time constant of 10 to 25 seconds, depending on the magnitude of exocytosis. Presynaptic loading of the nonhydrolyzable guanosine 5'-triphosphate (GTP) analog GTPgS or dynamin-1 proline-rich domain peptide abolished endocytosis. These compounds had no immediate effect on exocytosis, but caused a use-dependent rundown of exocytosis. Thus, the guanosine triphosphatase dynamin-1 is indispensable for vesicle endocytosis at this fast central nervous system (CNS) synapse.     

Ciguatoxin: isolation and chemical nature

Ciguatoxin, the agent responsible for ciguatera, a disease produced in humans from ingestion of certain fishes, has been isolated from specimens of the moray eel, Gymnothorax javanicus. The toxin is apparently a lipid containing quaternary nitrogen, hydroxyl, and carbonyl functions.