The waking action of histamine

Zusammenfassung Die i.v. Infusion von 1 mg Histamin-2 HCl in 30 ml bei einer konstanten Strömung von 1 ml/min während 30 min führt zu einer statistisch signifikanten Abnahme der spontanen kortikalen Delta-Aktivität beim Kaninchen. Dieser elektrographische Weck-Parameter, der gleichzeitig mit einer Desynchronisierung des EEG einhergeht, ist bedeutend grösser bei Kaninchen, die Histamin erhalten haben, als bei Kontrolltieren. Die Weckreaktion dauert nach Ende der Infusion weitere 30 min an. Gleichzeitig bewirkt Histamin ein geringfügiges, nicht signifikantes Absinken des arteriellen Blutdruckes, eine Zunahme der Herzfrequenz sowie ein leichtes Ansteigen der Atmungsfrequenz. Aus diesen Befunden geht hervor, dass Histamin bei unwichtigen visceralen Auswirkungen bei der Regulierung des Wach-Schlaf-Zustandes eine Rolle spielen könnte.     

Crystal symmetry and the reversibility of martensitic transformations

Martensitic transformations are diffusionless, solid-to-solid phase transitions, and have been observed in metals, alloys, ceramics and proteins. They are characterized by a rapid change of crystal structure, accompanied by the development of a rich microstructure. Martensitic transformations can be irreversible, as seen in steels upon quenching, or they can be reversible, such as those observed in shape-memory alloys. In the latter case, the microstructures formed on cooling are easily manipulated by loads and disappear upon reheating. Here, using mathematical theory and numerical simulation, we explain these sharp differences in behaviour on the basis of the change in crystal symmetry during the transition. We find that a necessary condition for reversibility is that the symmetry groups of the parent and product phases be included in a common finite symmetry group. In these cases, the energy barrier to lattice-invariant shear is generically higher than that pertaining to the phase change and, consequently, transformations of this type can occur with virtually no plasticity. Irreversibility is inevitable in all other martensitic transformations, where the energy barrier to plastic deformation (via lattice-invariant shears, as in twinning or slip) is no higher than the barrier to the phase change itself. Various experimental observations confirm the importance of the symmetry of the stable states in determining the macroscopic reversibility of martensitic transformations.     

Mutations in a new photoreceptor-pineal gene on 17p cause Leber congenital amaurosis

Leber congenital amaurosis (LCA, MIM 204000) accounts for at least 5% of all inherited retinal disease and is the most severe inherited retinopathy with the earliest age of onset. Individuals affected with LCA are diagnosed at birth or in the first few months of life with severely impaired vision or blindness, nystagmus and an abnormal or flat electroretinogram (ERG). Mutations in GUCY2D (ref. 3), RPE65 (ref. 4) and CRX (ref. 5) are known to cause LCA, but one study identified disease-causing GUCY2D mutations in only 8 of 15 families whose LCA locus maps to 17p13.1 (ref. 3), suggesting another LCA locus might be located on 17p13.1. Confirming this prediction, the LCA in one Pakistani family mapped to 17p13.1, between D17S849 and D17S960-a region that excludes GUCY2D. The LCA in this family has been designated LCA4 (ref. 6). We describe here a new photoreceptor/pineal-expressed gene, AIPL1 (encoding aryl-hydrocarbon interacting protein-like 1), that maps within the LCA4 candidate region and whose protein contains three tetratricopeptide (TPR) motifs, consistent with nuclear transport or chaperone activity. A homozygous nonsense mutation at codon 278 is present in all affected members of the original LCA4 family. AIPL1 mutations may cause approximately 20% of recessive LCA, as disease-causing mutations were identified in 3 of 14 LCA families not tested previously for linkage.     

EYS, encoding an ortholog of Drosophila spacemaker, is mutated in autosomal recessive retinitis pigmentosa

Using a positional cloning approach supported by comparative genomics, we have identified a previously unreported gene, EYS, at the RP25 locus on chromosome 6q12 commonly mutated in autosomal recessive retinitis pigmentosa. Spanning over 2 Mb, this is the largest eye-specific gene identified so far. EYS is independently disrupted in four other mammalian lineages, including that of rodents, but is well conserved from Drosophila to man and is likely to have a role in the modeling of retinal architecture.     

The Dynamics and Control of the Fractional Forms of Some Rational Chaotic Maps

This paper proposes three fractional discrete chaotic systems based on the Rulkov, Chang,and Zeraoulia–Sprott rational maps. The dynamics of the proposed maps are investigated by means of phase plots and bifurcations diagrams. Adaptive stabilization schemes are proposed for each of the three maps and the convergence of the states is established by using the Lyapunov method. Furthermore, a combination synchronization scheme is proposed whereby a combination of the fractional Rulkov and Chang maps is synchronized to the fractional Zeraoulia-Sprott map. Numerical results are used to confirm the findings of the paper.     

DNA primase acts as a molecular brake in DNA replication

A hallmark feature of DNA replication is the coordination between the continuous polymerization of nucleotides on the leading strand and the discontinuous synthesis of DNA on the lagging strand. This synchronization requires a precisely timed series of enzymatic steps that control the synthesis of an RNA primer, the recycling of the lagging-strand DNA polymerase, and the production of an Okazaki fragment. Primases synthesize RNA primers at a rate that is orders of magnitude lower than the rate of DNA synthesis by the DNA polymerases at the fork. Furthermore, the recycling of the lagging-strand DNA polymerase from a finished Okazaki fragment to a new primer is inherently slower than the rate of nucleotide polymerization. Different models have been put forward to explain how these slow enzymatic steps can take place at the lagging strand without losing coordination with the continuous and fast leading-strand synthesis. Nonetheless, a clear picture remains elusive. Here we use single-molecule techniques to study the kinetics of a multiprotein replication complex from bacteriophage T7 and to characterize the effect of primase activity on fork progression. We observe the synthesis of primers on the lagging strand to cause transient pausing of the highly processive leading-strand synthesis. In the presence of both leading- and lagging-strand synthesis, we observe the formation and release of a replication loop on the lagging strand. Before loop formation, the primase acts as a molecular brake and transiently halts progression of the replication fork. This observation suggests a mechanism that prevents leading-strand synthesis from outpacing lagging-strand synthesis during the slow enzymatic steps on the lagging strand.     

Epigenetic choreography of stem cells: the DNA demethylation episode of development

Reversible DNA methylation is a fundamental epigenetic manipulator of the genomic information in eukaryotes. DNA demethylation plays a very significant role during embryonic development and stands out for its contribution in molecular reconfiguration during cellular differentiation for determining stem cell fate. DNA demethylation arbitrated extensive make-over of the genome via reprogramming in the early embryo results in stem cell plasticity followed by commitment to the principal cell lineages. This article attempts to highlight the sequential phases and hierarchical mode of DNA demethylation events during enactment of the molecular strategy for developmental transition. A comprehensive knowledge regarding the pattern of DNA demethylation during embryogenesis and organogenesis and study of the related lacunae will offer exciting avenues for future biomedical research and stem cell-based regenerative therapy.     

Long-term evolution and transmission dynamics of swine influenza A virus

Swine influenza A viruses (SwIV) cause significant economic losses in animal husbandry as well as instances of human disease and occasionally give rise to human pandemics, including that caused by the H1N1/2009 virus. The lack of systematic and longitudinal influenza surveillance in pigs has hampered attempts to reconstruct the origins of this pandemic. Most existing swine data were derived from opportunistic samples collected from diseased pigs in disparate geographical regions, not from prospective studies in defined locations, hence the evolutionary and transmission dynamics of SwIV are poorly understood. Here we quantify the epidemiological, genetic and antigenic dynamics of SwIV in Hong Kong using a data set of more than 650 SwIV isolates and more than 800 swine sera from 12?years of systematic surveillance in this region, supplemented with data stretching back 34?years. Intercontinental virus movement has led to reassortment and lineage replacement, creating an antigenically and genetically diverse virus population whose dynamics are quantitatively different from those previously observed for human influenza viruses. Our findings indicate that increased antigenic drift is associated with reassortment events and offer insights into the emergence of influenza viruses with epidemic potential in swine and humans.