Vertebrate circadian rhythms: Retinal and extraretinal photoreception

Summary ERRs Both the pineal and the SCN are elements of the vertebrate multioscillator system although the relative importance of these 2 areas probably varies between, and possibly within, the different vertebrate classes. Extraretinal photoreception is a universal feature of submammalian vertebrates, and possibly of neonatal mammals, but is absent in adult mammals. Although the pineal systems of sumammalian vertebrates are photosensitive, the pineal system has been directly implicated as an extraocular site for the perception of entraining light cycles only in amphibians. In all other submammalian vertebrates extraretinal entrainment can occur in the absence of the pineal system although it is certainly conceivable that the pineal system may act as an alternate route of photoreception. These extraretinal-extrapineal receptors are located within the brain but the exact location(s) of these receptors within the brain is unknown. The hypothalamus would be likely area for this extraretinal photoreception, however, for several reasons: 1. Neurophysiological studies have identified light sensitive neurons in the frog's hypothalamus⁴³. 2. The avian hypothalamus is a site of photoperiodic photoreception^100–103. 3. The only other light sensitive structures known in vertebrates—the pineal system and the lateral eyes—are all derived embryologically from the hypothalamus. 4. The hypothalamus appears to be the site of a circadian clock and there may be advantages in having the photoreceptors and the clock anatomically close to one another. These considerations, of course, do not exclude the possibility that other brain areas may be involved as well. The reason behind the loss of extraretinal photoreception in mammals is uncertain. The shift to exclusive retinal photoreception in mammals may have been dictated by the extensive reorganization that occurred during the evolution of the mammalian brain. Or, perhaps, the increased size of the mammalian skull and overlying tissue made direct photoreception difficult and necessitated a shift to retinal photoreception. The persistence of extraretinal photoreceptors in submammalian vertebrates, however, underscores their importance in the sensory repertoire of vertebrates.     

Chemical components of the rectal gland secretions of maleDacus cucurbitae,the melon fly

Summary The volatile constituents of the rectal gland secretion of maleDacus cucurbitae have been shown to contain 2-methoxy-N-3-methylbutyl acetamide together with 2 other amides, 3 pyrazine derivatives and 2-ethoxybenzoic acid. Excised male rectal glands have been demonstrated to elicit strong responses from female melon flies.Acknowledgment. We thank Dr P. Howse for valuable discussions and advice.     

Night shift paralysis

Summary 12% of night nurses surveyed claimed to have suffered from a totally incapacitating paralysis that may be related to sleep paralysis, and contribute to impaired levels of safety on the night shift. The incidence of this paralysis is shown to be age-related, largely confined to the early hours of the morning, and to increase over consecutive night shifts.Acknowledgments. We wish to dedicate this paper to Professor Dr Günther Hildebrandt, Director of the Institut für Arbeitsphysiologie und Rehabilitationsforschung, University of Marburg/Lahn in honor of his 60th birthday. We also wish to thank the Nursing Officers and nurses concerned for their help in this study.     

Polymorphism and absence of Leu-enkephalin sequences in proenkephalin genes in Xenopus laevis

The structures of the genes coding for the opioid peptide precursors proopiomelanocortin, proenkephalin (proenkephalin A) and prodynorphin (proenkephalin B), are known for some mammalian species. To gain insight into the evolutionary history of these precursors, we have examined the proenkephalin gene in the South African clawed toad, Xenopus laevis, which diverged from the principal line of vertebrate evolution some 350 Myr ago. The human proenkephalin gene consists of four exons, of which the main exon (exon IV) contains all known biologically active peptides--six Met-enkephalin sequences and one Leu-enkephalin sequence. We report here the primary structures of the putative main exons of two proenkephalin genes in X. laevis, each of which codes for seven Met-enkephalin sequences but no Leu-enkephalin, indicating that Met-enkephalin preceded Leu-enkephalin in the evolution of the proenkephalin gene. The organization of the main exons of the toad genes is remarkably similar to that of the human gene and conserved regions provide evidence for functionally significant structures. We also detect a polymorphism in one of the toad proenkephalin genes, mapping 1.5 kilobases (kb) 5' of the main exon; it is caused by an insertion/deletion of a 1-kb repetitive sequence which has the characteristics of a transposable element.     

Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis

The normal plasma protein serum amyloid P component (SAP) binds to fibrils in all types of amyloid deposits, and contributes to the pathogenesis of amyloidosis. In order to intervene in this process we have developed a drug, R-1-[6-[R-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid, that is a competitive inhibitor of SAP binding to amyloid fibrils. This palindromic compound also crosslinks and dimerizes SAP molecules, leading to their very rapid clearance by the liver, and thus produces a marked depletion of circulating human SAP. This mechanism of drug action potently removes SAP from human amyloid deposits in the tissues and may provide a new therapeutic approach to both systemic amyloidosis and diseases associated with local amyloid, including Alzheimer's disease and type 2 diabetes.     

The role of volatiles in magma chamber dynamics

Many andesitic volcanoes exhibit effusive eruption activity, with magma volumes as large as 10(7)-10(9) m(3) erupted at rates of 1-10 m(3) x s(-1) over periods of years or decades. During such eruptions, many complex cycles in eruption rates have been observed, with periods ranging from hours to years. Longer-term trends have also been observed, and are thought to be associated with the continuing recharge of magma from deep in the crust and with waning of overpressure in the magma reservoir. Here we present a model which incorporates effects due to compressibility of gas in magma. We show that the eruption duration and volume of erupted magma may increase by up to two orders of magnitude if the stored internal energy associated with dissolved volatiles can be released into the magma chamber. This mechanism would be favoured in shallow chambers or volatile-rich magmas and the cooling of magma by country rock may enhance this release of energy, leading to substantial increases in eruption rate and duration.     

Mutations in CLCN2 encoding a voltage-gated chloride channel are associated with idiopathic generalized epilepsies

Idiopathic generalized epilepsy (IGE) is an inherited neurological disorder affecting about 0.4% of the world's population. Mutations in ten genes causing distinct forms of idiopathic epilepsy have been identified so far, but the genetic basis of many IGE subtypes is still unknown. Here we report a gene associated with the four most common IGE subtypes: childhood and juvenile absence epilepsy (CAE and JAE), juvenile myoclonic epilepsy (JME), and epilepsy with grand mal seizures on awakening (EGMA; ref. 8). We identified three different heterozygous mutations in the chloride-channel gene CLCN2 in three unrelated families with IGE. These mutations result in (i) a premature stop codon (M200fsX231), (ii) an atypical splicing (del74-117) and (iii) a single amino-acid substitution (G715E). All mutations produce functional alterations that provide distinct explanations for their pathogenic phenotypes. M200fsX231 and del74-117 cause a loss of function of ClC-2 channels and are expected to lower the transmembrane chloride gradient essential for GABAergic inhibition. G715E alters voltage-dependent gating, which may cause membrane depolarization and hyperexcitability.