The absence of melanopsin alters retinal clock function and dopamine regulation by light

The retinal circadian clock is crucial for optimal regulation of retinal physiology and function, yet its cellular location in mammals is still controversial. We used laser microdissection to investigate the circadian profiles and phase relations of clock gene expression and Period gene induction by light in the isolated outer (rods/cones) and inner (inner nuclear and ganglion cell layers) regions in wild-type and melanopsin-knockout (Opn ₄ ^?/? ) mouse retinas. In the wild-type mouse, all clock genes are rhythmically expressed in the photoreceptor layer but not in the inner retina. For clock genes that are rhythmic in both retinal compartments, the circadian profiles are out of phase. These results are consistent with the view that photoreceptors are a potential site of circadian rhythm generation. In mice lacking melanopsin, we found an unexpected loss of clock gene rhythms and of the photic induction of Per1-Per2 mRNAs only in the outer retina. Since melanopsin ganglion cells are known to provide a feed-back signalling pathway for photic information to dopaminergic cells, we further examined dopamine (DA) synthesis in Opn ₄ ^?/? mice. The lack of melanopsin prevented the light-dependent increase of tyrosine hydroxylase (TH) mRNA and of DA and, in constant darkness, led to comparatively high levels of both components. These results suggest that melanopsin is required for molecular clock function and DA regulation in the retina, and that Period gene induction by light is mediated by a melanopsin-dependent, DA-driven signal acting on retinal photoreceptors.     

A copy number variation morbidity map of developmental delay

To understand the genetic heterogeneity underlying developmental delay, we compared copy number variants (CNVs) in 15,767 children with intellectual disability and various congenital defects (cases) to CNVs in 8,329 unaffected adult controls. We estimate that ～14.2% of disease in these children is caused by CNVs >400 kb. We observed a greater enrichment of CNVs in individuals with craniofacial anomalies and cardiovascular defects compared to those with epilepsy or autism. We identified 59 pathogenic CNVs, including 14 new or previously weakly supported candidates, refined the critical interval for several genomic disorders, such as the 17q21.31 microdeletion syndrome, and identified 940 candidate dosage-sensitive genes. We also developed methods to opportunistically discover small, disruptive CNVs within the large and growing diagnostic array datasets. This evolving CNV morbidity map, combined with exome and genome sequencing, will be critical for deciphering the genetic basis of developmental delay, intellectual disability and autism spectrum disorders.     

USING DISPLACED CONE REPRESENTATION IN DEA MODELS FOR NONDOMINATED SOLUTIONSIN MULTIOBJECTIVE PROGRAMMING

1.IlltroductionBowlin,etal.[2]extendedtheearlierworkofBowlinetal.11]aspartofaresponsetowhatseemstobeagrowinginterestintheuseofefficiencydominance--asreflected,forexampleintheworkofLoved[7],TulkensandVandenEeckaut[lo]andtheirassociates.ThefocusinBowlinetal.[2]turnedtotheuseofan11metricasabasisfor(1)measuringtheamountofefficiencydominancethatmightbepresentinanyDecisionMakingUnit(DMU)aswellasfor(2)dealingwithproblemsinvolvedinthepossiblepresenceofslackswithnon-zerovalues,--whichareimportantas…     

Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis.

Sequence variation in human genes is largely confined to single-nucleotide polymorphisms (SNPs) and is valuable in tests of association with common diseases and pharmacogenetic traits. We performed a systematic and comprehensive survey of molecular variation to assess the nature, pattern and frequency of SNPs in 75 candidate human genes for blood-pressure homeostasis and hypertension. We assayed 28 Mb (190 kb in 148 alleles) of genomic sequence, comprising the 5' and 3' untranslated regions (UTRs), introns and coding sequence of these genes, for sequence differences in individuals of African and Northern European descent using high-density variant detection arrays (VDAs). We identified 874 candidate human SNPs, of which 22% were confirmed by DNA sequencing to reveal a discordancy rate of 21% for VDA detection. The SNPs detected have an average minor allele frequency of 11%, and 387 are within the coding sequence (cSNPs). Of all cSNPs, 54% lead to a predicted change in the protein sequence, implying a high level of human protein diversity. These protein-altering SNPs are 38% of the total number of such SNPs expected, are more likely to be population-specific and are rarer in the human population, directly demonstrating the effects of natural selection on human genes. Overall, the degree of nucleotide polymorphism across these human genes, and orthologous great ape sequences, is highly variable and is correlated with the effects of functional conservation on gene sequences.     

Germination inhibition activity of a naturally occurring lignan fromAegilops ovata L. in green and infrared light

Summary The naturally occurring lignan, monoepoxylignanolide (MEL) fromAegilops ovata L., inhibits germination of lettuce achenes (seeds) in incandescent light but not in the dark. The action spectrum after preincubation of MEL in darkness shows inhibition in the regions of 399 nm and 712–804 nm, but after pretreatment with incandescent light inhibition is seen at 500–577 nm and 712–804 nm. The infrared inhibition by MEL is not reversible by red light. The pretreatment of MEL with incandescent light gives rise to a photoproduct which, together with MEL itself, inhibits the germination of lettuce achenes in the dark.     

Complete mitochondrial genome sequences of two extinct moas clarify ratite evolution

The origin of the ratites, large flightless birds from the Southern Hemisphere, along with their flighted sister taxa, the South American tinamous, is central to understanding the role of plate tectonics in the distributions of modern birds and mammals. Defining the dates of ratite divergences is also critical for determining the age of modern avian orders. To resolve the ratite phylogeny and provide biogeographical data to examine these issues, we have here determined the first complete mitochondrial genome sequences of any extinct taxa--two New Zealand moa genera--along with a 1,000-base-pair sequence from an extinct Madagascan elephant-bird. For comparative data, we also generated 12 kilobases of contiguous sequence from the kiwi, cassowary, emu and two tinamou genera. This large dataset allows statistically precise estimates of molecular divergence dates and these support a Late Cretaceous vicariant speciation of ratite taxa, followed by the subsequent dispersal of the kiwi to New Zealand. This first molecular view of the break-up of Gondwana provides a new temporal framework for speciation events within other Gondwanan biota and can be used to evaluate competing biogeographical hypotheses.