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Biomedical subjects

Ben Collins

Publications and source records attributed to Ben Collins.

6 recordsLinked to original sources
PubMed2007

Even a stopped clock tells the right time twice a day: circadian timekeeping in Drosophila.

"Even a stopped clock tells the right time twice a day, and for once I'm inclined to believe Withnail is right. We are indeed drifting into the arena of the unwell... What we need is harmony. Fresh air. Stuff like that" "Bruce Robinson (1986, ref. 1)". Although a stopped Drosophila clock probably does not tell the right time even once a day, recent findings have demonstrated that accurate circadian time-keeping is dependent on harmony between groups of clock neurons within the brain. Furthermore, when harmony between the environment and the endogenous clock is lost, as during jet lag, we definitely feel unwell. In this review, we provide an overview of the current understanding of circadian rhythms in Drosophila, focussing on recent discoveries that demonstrate how approximately 100 neurons within the Drosophila brain control the behaviour of the whole fly, and how these rhythms respond to the environment.

Adaptation, Biological↗
PubMed2006

Keeping time without a clock.

The accepted dogma in circadian biology is that the transcription factor CLOCK lies at the heart of the molecular clock that drives behavioral and molecular rhythms. In this issue of Neuron, the generation of CLOCK-deficient mice with only subtle clock defects by DeBruyne et al. shakes up this view of the mammalian clock.

Animals↗
PubMed2006

Drosophila CRYPTOCHROME is a circadian transcriptional repressor.

BACKGROUND: Although most circadian clock components are conserved between Drosophila and mammals, the roles assigned to the CRYPTOCHROME (CRY) proteins are very different: Drosophila CRY functions as a circadian photoreceptor, whereas mammalian CRY proteins (mCRY1 and 2) are transcriptional repressors essential for molecular clock oscillations. RESULTS: Here we demonstrate that Drosophila CRY also functions as a transcriptional repressor. We found that RNA levels of genes directly activated by the transcription factors CLOCK (CLK) and CYCLE (CYC) are derepressed in cry(b) mutant eyes. Conversely, while overexpression of CRY and PERIOD (PER) in the eye repressed CLK/CYC activity, neither PER nor CRY repressed individually. Drosophila CRY also repressed CLK/CYC activity in cell culture. Repression by CRY appears confined to peripheral clocks, since neither cry(b) mutants nor overexpression of PER and CRY together in pacemaker neurons significantly affected molecular or behavioral rhythms. Increasing CLK/CYC activity by removing two repressors, PER and CRY, led to ectopic expression of the timeless clock gene, similar to overexpression of Clk itself. CONCLUSIONS: Drosophila CRY functions as a transcriptional repressor required for the oscillation of peripheral circadian clocks and for the correct specification of clock cells.

ARNTL Transcription Factors↗
PubMed2004

An abundant placental transcript containing an IAP-LTR is allelic to mouse pregnancy-specific glycoprotein 23 (Psg23): cloning and genetic analysis.

Several families of endogenous retroviruses (ERVs) are expressed in mammalian placental tissues, and are implicated in aspects of placental development and function. We characterized the structure of abundant ERV-related transcripts in mouse placenta. In addition to the 7 kb full-length type I and 5 kb type I deleted intracisternal A-particle (IAP) transcripts, we identified and cloned an abundant 2 kb transcript encoding a novel member of the pregnancy-specific glycoprotein (Psg) gene family, which contains an IAP long terminal repeat (LTR) in the 3' untranslated region (UTR). The polyadenylation signal for the transcript is provided by the inserted LTR sequence. This sequence is allelic to Psg23 and is therefore denoted as Psg23(LTR). The transcript encodes a protein of 471 amino acids and has a domain organisation similar to previously described Psg proteins. Modelling of the protein N-domain produced a structure in good agreement with an existing crystalline structure for mouse sCEACAM1a. The LTR insertion is widely distributed among inbred mouse strains but is not found in 129/sv, CBA/2, or in wild mice. Cloning of the genomic region downstream of the LTR insertion site from the C57Bl/6J strain indicates that the insertion consists of a solo LTR without additional IAP sequence, and identified the original Psg23 polyadenylation signal sequence downstream of the insertion site. Psg23(LTR) was mapped to proximal chromosome 7 using the European collaborative interspecific mouse backcross (EUCIB) panel, and to yeast artificial chromosome (YAC) E072, which contains other members of the Psg gene family, by polymerase chain reaction (PCR). Northern blot analysis of RNA from adult and fetal mouse tissues and in situ hybridization to mid-gestation mouse embryos indicated that Psg23(LTR) is expressed predominantly in placental spongiotrophoblast. We detected a small, but statistically non-significant, bias in favour of transmission of Psg23(LTR) to the offspring of heterozygous parents. However, a larger study would be required to determine whether this allele is selectively advantageous to the developing embryo.

Alleles↗