Human Papillomaviruses in Buschke-Lowenstein Tumors: Physical State of the DNA and Identification of a Tandem Duplication in the Noncoding Region of a Human Papillomavirus 6 Subtype

Six Buschke-Löwenstein tumors, i.e., highly differentiated squamous cell tumors of the genital region, were shown to contain human papillomavirus 6 (HPV 6) or HPV 11 genomes. The viral DNA was found in an episomal state, including a very small fraction of circular oligomers. HPV 6a and HPV 6d genomes were cloned from two of the tumors. Comparison with HPV 6b, cloned from a benign genital wart (E. -M. de Villiers, L. Gissmann, and H. zur Hausen, J. Virol. 40:932-935, 1981) by restriction mapping and partial sequence analysis, revealed a very high degree of homology with the different HPV 6 subtypes. A tandem duplication of 459 base pairs within the noncoding region of the genome was found in the new subtype HPV 6d. This structural rearrangement in a region containing the putative control elements for early gene transcription might influence the biological potential of that virus. No evidence for rearrangement of this region was found in the HPV DNA from the five other tumors

The search for infectious causes of human cancers: Where and why

AbstractSlightly more than 20% of the global cancer burden can presently be linked to infectious agents, including viruses, bacteria and parasites. This manuscript analyzes reasons for their relatively late discovery and highlights epidemiological observations that may point to an involvement of additional infectious agents in specific human cancers. Emphasis is placed on hematopoietic malignancies, breast and colorectal cancers, but also basal cell carcinomas of the skin and lung cancers in non-smokers

El significado de la disposición de las quetas en las sistemática de los Maldánidos (Annelida: Maldanidae)

Maldanids are usually divided into several subfamilies: Euclymeninae, Lumbriclymeninae, Maldaninae, Nicomachinae, Rhodininae, Clymenurinae, Notoproctinae, and Boguinae. The taxonomy of maldanids and the delimination of these taxa are mainly based on head morphology, total number of segments, chaetal structure, shape of the pygidium, and position of the anus. The maldanid ingroup relationships, as well as the monophyly of the proposed subfamilies, have so far not been investigated. Pilgrim (1977) described a shift of the notopodial chaetal rows from a transverse direction in anterior chaetigers to a more longitudinal one in posterior chaetigers in Clymene torquata (Leidy, 1855) and Euclymene oerstedii (Claparède, 1863), both belonging to the Euclymeninae. We investigated several maldanid species to assess the usefulness of this character for maldanid systematics and used 3D-reconstruction techniques to reveal the complete geometry of the chaetal sacs. Our investigation shows that a shift is apparent in Euclymene, Axiothella, Johnstonia (all Euclymeninae) and Clymenura (Clymenurinae), but absent in species like Maldane sarsi (Malmgren, 1865), Metasychis disparidentata (Moore, 1904) (both Maldaninae) and Petaloproctus borealis Ardwisson, 1906 (Nicomachinae). The shift is not typical for sedentary polychaetes and is apomorphic within maldanid polychaetes. It thus argues for a close relationship between Euclymeninae and Clymenurinae. The investigation of further maldanid species of different subfamilies may shed additional light on maldanid systematics.Los Maldánidos se clasifican usualmente en ocho subfamilias: Euclymeninae, Lumbriclymeninae, Maldaninae, Nicomachinae, Rhodininae, Clymenurinae, Notoproctinae, y Boguinae. La taxonomía de esta familia está basada en la morfología del prostómio, el número total de segmentos, la estructura de las quetas, la forma del pigidio y la posición del ano. Sin embargo, las relaciones dentro del grupo de los maldánidos , así como la monofília de las subfamilias propuestas, no han sido aún investigadas. Pilgrim (1977) describió en Clymene torquata (Leidy, 1855) y Euclymene oerstedii (Claparède, 1863), ambos pertenecientes a Euclymeninae, un cambio en la orientación de las filas de quetas notopodiales desde una poción transversal en los setígeros anteriores a una posición más longitudinal en los setígeros posteriores. En este trabajo se ha investigado el carácter anterior en diversas especies de maldánidos para ver si podría ser usado en la sistemática del grupo, usando reconstrucciones en tres dimensiones para observar la completa geometría de las bolsas de quetas, Nuestras investigaciones muestran que dichos cambios son aparentes en Euclymene, Axiothella, Johnstonia (todos Euclymeninae) y en Clymenura (Clymenurinae), pero no se presentan en especies como Maldane sarsi (Malmgren, 1865), Metasychis disparidentata (Moore, 1904) (ambas Maldaninae) y Petaloproctus borealis Ardwisson, 1906 (Nicomachinae). Este cambio no es típico de poliquetos sedentarios y es apomorfico dentro de los maldánidos. Todo ello lleva a argumentar una estrecha relación entre Euclymeninae y Clymenurinae. Futuras investigaciones en otras especies de maldánidos pertenecientes a otras subfamilias podría aportar aún mas luz a la sistemática de esta familia de poliquetos. &nbsp

The rhodopsin-retinochrome system for retinal re-isomerization predates the origin of cephalopod eyes

Background: The process of photoreception in most animals depends on the light induced isomerization of the chromophore retinal, bound to rhodopsin. To re-use retinal, the all-trans-retinal form needs to be re-isomerized to 11-cis-retinal, which can be achieved in different ways. In vertebrates, this mostly includes a stepwise enzymatic process called the visual cycle. The best studied re-isomerization system in protostomes is the rhodopsin-retinochrome system of cephalopods, which consists of rhodopsin, the photoisomerase retinochrome and the protein RALBP functioning as shuttle for retinal. In this study we investigate the expression of the rhodopsin-retinochrome system and functional components of the vertebrate visual cycle in a polyplacophoran mollusk, Leptochiton asellus, and examine the phylogenetic distribution of the individual components in other protostome animals. Results: Tree-based orthology assignments revealed that orthologs of the cephalopod retinochrome and RALBP are present in mollusks outside of cephalopods. By mining our dataset for vertebrate visual cycle components, we also found orthologs of the retinoid binding protein RLBP1, in polyplacophoran mollusks, cephalopods and a phoronid. In situ hybridization and antibody staining revealed that L. asellus retinochrome is co-expressed in the larval chiton photoreceptor cells (PRCs) with the visual rhodopsin, RALBP and RLBP1. In addition, multiple retinal dehydrogenases are expressed in the PRCs, which might also contribute to the rhodopsin-retinochrome system. Conclusions: We conclude that the rhodopsin-retinochrome system is a common feature of mollusk PRCs and predates the origin of cephalopod eyes. Our results show that this system has to be extended by adding further components, which surprisingly, are shared with vertebrates.publishedVersio

Comparative analysis defines a broader FMRFamide-gated sodium channel family and determinants of neuropeptide sensitivity

FMRFamide (Phe-Met-Arg-Phe-amide, FMRFa) and similar neuropeptides are important physiological modulators in most invertebrates, but the molecular basis of FMRFa activity at its receptors is unknown. We therefore sought to identify the molecular determinants of FMRFa potency against one of its native targets, the excitatory FMRFa-gated sodium channel (FaNaC) from gastropod mollusks. Using molecular phylogenetics and electrophysiological measurement of neuropeptide activity, we identified a broad FaNaC family that includes mollusk and annelid channels gated by FMRFa, FVRIamides, and/or Wamides (or myoinhibitory peptides). A comparative analysis of this broader FaNaC family and other channels from the overarching degenerin (DEG)/epithelial sodium channel (ENaC) superfamily, incorporating mutagenesis and experimental dissection of channel function, identified a pocket of amino acid residues that determines activation of FaNaCs by neuropeptides. Although this pocket has diverged in distantly related DEG/ENaC channels that are activated by other ligands but enhanced by FMRFa, such as mammalian acid-sensing ion channels, we show that it nonetheless contains residues that determine enhancement of those channels by similar peptides. This study thus identifies amino acid residues that determine FMRFa neuropeptide activity at FaNaC receptor channels and illuminates the evolution of ligand recognition in one branch of the DEG/ENaC superfamily of ion channels.publishedVersio

The development of early pioneer neurons in the annelid Malacoceros fuliginosus

Background Nervous system development is an interplay of many processes: the formation of individual neurons, which depends on whole-body and local patterning processes, and the coordinated growth of neurites and synapse formation. While knowledge of neural patterning in several animal groups is increasing, data on pioneer neurons that create the early axonal scaffold are scarce. Here we studied the first steps of nervous system development in the annelid Malacoceros fuliginosus. Results We performed a dense expression profiling of a broad set of neural genes. We found that SoxB expression begins at 4 h postfertilization, and shortly later, the neuronal progenitors can be identified at the anterior and the posterior pole by the transient and dynamic expression of proneural genes. At 9 hpf, the first neuronal cells start differentiating, and we provide a detailed description of axonal outgrowth of the pioneer neurons that create the primary neuronal scaffold. Tracing back the clonal origin of the ventral nerve cord pioneer neuron revealed that it is a descendant of the blastomere 2d (2d221), which after 7 cleavages starts expressing Neurogenin, Acheate-Scute and NeuroD. Conclusions We propose that an anterior and posterior origin of the nervous system is ancestral in annelids. We suggest that closer examination of the first pioneer neurons will be valuable in better understanding of nervous system development in spirally cleaving animals, to determine the potential role of cell-intrinsic properties in neuronal specification and to resolve the evolution of nervous systems.publishedVersio

The visual pigment xenopsin is widespread in protostome eyes and impacts the view on eye evolution

Photoreceptor cells in the eyes of Bilateria are often classified into microvillar cells with rhabdomeric opsin and ciliary cells with ciliary opsin, each type having specialized molecular components and physiology. First data on the recently discovered xenopsin point towards a more complex situation in protostomes. In this study, we provide clear evidence that xenopsin enters cilia in the eye of the larval bryozoan Tricellaria inopinata and triggers phototaxis. As reported from a mollusc, we find xenopsin coexpressed with rhabdomeric-opsin in eye photoreceptor cells bearing both microvilli and cilia in larva of the annelid Malacoceros fuliginosus. This is the first organism known to have both xenopsin and ciliary opsin, showing that these opsins are not necessarily mutually exclusive. Compiling existing data, we propose that xenopsin may play an important role in many protostome eyes and provides new insights into the function, evolution, and possible plasticity of animal eye photoreceptor cells.publishedVersio

原著

摘出ラット上頸交感神経節を用いて,刺激頻度と薬物作用との関係を検討し,次の結果を得た。1.Hexamethonium,d-Tubocurarine,PhysostigmineおよびParaoxon作用下では,神経節伝達抑制作用が低頻度刺激よりも高頻度刺激により増強された。このような薬物効果をType Aとした。2.Adrenaline(Adr.),Nor-Adrenaline(Nor-Adr),MgCl_2,MnCl_2ならびにCa^-deficit Ringer(0.1〜0.4mM CaCl_2)では,低頻度刺激時にみられた抑制効果が高頻度刺激下で著しく回復され,この効果をType Bとした。3.ProcaineおよびPropranolol作用下の抑制効果は,刺激頻度の多少にほとんど影響されなかった。この効果をType Cとした。4.Adr.,Nor-Adr.のType B効果はPhentolamineにより拮抗されたが,ほとんどPropranololの影響をうけなかった。MgCl_2,MnCl_2およびCa^#-deficit効果は,α-,およびβ-効果遮断薬により影響されなかった。5.Type B作用群薬物の効果は,high Ca^-Ringer(9mM CaCl_2)で消失され,low Ca^-Ringer液中で増強された。6.Ringer液中のNa^+およびK^+イオンの増減ならびにOuabain(10μM)はType B効果に影響を与えなかった。7.Sucrose-gap法による実験で,Type B作用群薬物は単発刺激による神経節のspike potentialを消失し,比較的大きなsynaptic potentialを生じた。このsynaptic potentialは,300msec以下の刺激間隔で与えた2発刺激により容易にspike potentialに発展した。また高頻度刺激によっても漸次増大するspike potentialが容易に発生した。8.Type B作用群薬物の作用機構についてとくに神経終末からの伝達物質遊離抑制面から考察した。The relationship between the rate of stimulation and effects of drugs on the superior cervical ganglion was investigated. Under the effect of hexamethonium, d-tubocu-rarine, physostigmine or paraoxon, ganglionic transmission was blocked more effectively with higher rate of stimulation than lower rate of stimulation (Type A drugs). Under the effect of adrenaline, noradrenaline, MgCl_2, MnCl_2 or Ca^-deficit Ringer (0.1-0.4mM CaCl_2,) solution, ganglionic transmission was depressed with lower rate of stimulation, but it was restored with higher rate of stimulation (Type B drugs). The inhibitory effect of procaine and propranolol on the ganglionic transmission was not affected by frequency change in transmission (Type C drugs). The effect of adrenaline or noradrenaline, those belong to the type B group, was blocked by phentolamine but not by propranolol. Phentolamine and propranolol had no effect on the action of MgCl_2, MnCl_2 and Ca^-deficit Ringer solution. The effect of the type B group drugs was decreased in Ringer solution containing higher concentration of Ca^ and augmented in Ringer solution containing lower concentration of Ca^. The effect of the type B group drugs was not affected by increasing or decreasing of the concentration of Na^+ or K^+ in Ringer solution. Ouabain (10μM) had no effect on the action of the type B drugs. By means of the sucrose-gap method, the spike potentials evoked by applying single stimulation were transferred to the synaptic potentials under the influence of the type B drugs. When the synaptic potential was evoked by the doubleshock stimuli of an interval shorter than 300 msec, the synaptic potential easily devoloped to the spike potential. In this work, the mechanism of action of the type B drugs was discussed on the standpoint of the depressed transmitter release

Early divergence, broad distribution, and high diversity of animal chitin synthases

Even though chitin is one of themost abundant biopolymers in nature, current knowledge on chitin formation is largely based only on data from fungi and insects. This study reveals unanticipated broad taxonomic distribution and extensive diversification of chitin synthases (CSs) in Metazoa, shedding newlight on the relevance of chitin in animals and suggesting unforeseen complexity of chitin synthesis in many groups. We uncovered robust orthologs to insect type CSs in several representatives of deuterostomes, which generally are not thought to possess chitin. This suggests a broader distribution and function of chitin in this branch of the animal kingdom. We characterize a new CS type present not only in basal metazoans such as sponges and cnidarians but also in several bilaterian representatives. Themost extensive diversification of CSs took place during emergence of lophotrochozoans, the third large group of protostomes next to arthropods and nematodes, resulting in coexistence of up to ten CS paralogs inmolluscs. Independent fusion to different kinds of myosinmotor domains in fungi and lophotrochozoans points toward high relevance of CS interaction with the cytoskeleton for fine-tuned chitin secretion. Given the fundamental role that chitin plays in themorphology of many animals, the here presented CS diversification revealsmany evolutionary complexities. Our findings strongly suggest a very broad andmultifarious occurrence of chitin and question an ancestral role as cuticular component. The molecular mechanisms underlying regulation of animal chitin synthesis are most likely far more complex and diverse than existing data from insects suggest