Long non-coding RNA PVT1 promotes malignancy in human endometrial carcinoma cells through negative regulation of miR-195-5p

The plasmacytoma variant translocation 1 (PVT1)¹ gene is a long non-coding RNA (lncRNA)² that has been shown to be an oncogene in many cancers. Herein, the function and potential molecular mechanisms connecting PVT1 and miR-195-5p were elucidated in endometrial cancer cell lines. Quantitative real-time PCR and fluorescence in situ hybridization (FISH)³ demonstrated that PVT1 is up-regulated concomitant with miR-195-5p down-regulation in human endometrial carcinoma tissues. PVT1 knockdown inhibited cell proliferation, migration, and invasion while facilitating apoptosis of endometrial cancer cells. Moreover, restoration of miR-195-5p due to PVT1 knockdown exerted tumor-suppressive functions. We observed that PVT1 promotes malignant cell behavior by decreasing miR-195-5p expression. Binding of PVT1 and miR-195-5p was confirmed using luciferase assays. Furthermore, expression of miR-195-5p negatively correlates with PVT1 expression. At the molecular level, either PVT1 knockdown or miR-195-5p overexpression resulted in a decrease of acidic fibroblast growth factor receptor (FGFR1)⁴ and basic fibroblast growth factor (FGF2).⁵ FGFR1 and FGF2 are targets of miR-195-5p that play a critical role in endometrial carcinoma by activating PI3K/AKT and MAPK/Erk pathways. Remarkably, PVT1 knockdown combined with miR-195-5p overexpression led to tumor regression in vivo. Overall, these results depict a novel pathway mediated by PVT1 in endometrial carcinoma, which may have potential application for endometrial carcinoma therapy.     

Control of estrus in bos indicus and bos taurus heifers with prostaglandin F2 alpha

Lutalyse^*, a commercial preparation of prostaglandin F_2a was injected intramuscularly into nulliparous heifers of the German Brown, Holstein—Friesian and White Fulani cattle. Two injections, 25mg/animal each time, were given at intervals of 12 days. All the heifers were inseminated 80h after the second injection. Heifers that were cycling responded well to the treatment and had a higher conception rate than the controls.     

Structural Ensemble Modulation upon Small-Molecule Binding to Disordered Proteins

Over the past decade, there has been a growing interest in investigating whether disordered proteins can be targeted for clinical purposes using small molecules [1], [2], [3], [4], [5], [6], [7], [8]. While small-molecule binding to disordered proteins can be seen as unorthodox, examples of this phenomenon have been reported. In order to rationalize these observations, a variety of models are emerging, sometimes in apparent contradiction. Here, we offer a “structural ensemble modulation” view as an attempt to clarify the language, organize concepts, and facilitate the comparison of different studies. In doing so, we hope to promote the understanding of the general principles underlying this phenomenon toward the development of novel therapeutic compounds targeting disordered proteins, which are prevalent in a wide range of human diseases [1], [2], [3], [4], [5], [6], [7], [8].     

The power of small changes: Comprehensive analyses of microbial dysbiosis in breast cancer

Disparate occurrence of breast cancer remains an intriguing question since only a subset of women with known risk factors develop cancer. Recent studies suggest an active role of local and distant microbiota in breast cancer initiation, progression, and overall prognosis. A dysbiotic microbiota predisposes the body to develop cancer by inducing genetic instability, initiating DNA damage and proliferation of the damaged progeny, eliciting favorable immune response, metabolic dysregulation and altered response to therapy. In this review, we present our analyses of the existing datasets and discuss the local dysbiosis observed in breast cancer patients and different aspects of breast carcinogenesis that can be potentially influenced by local breast microbiota. Striking differences between microbial community compositions in breast of cancer patients compared to healthy individuals were noted. Differences in microbiome were also apparent between benign and malignant disease and between nipple aspirate fluid of healthy individuals and breast survivors. We also discuss the identification of distinct bacterial, fungal, viral as well as parasite signatures for breast cancer. These microbes are capable of producing numerous secondary metabolites that can act as signaling mediators effecting breast cancer progression. We review how microbes potentially alter response to therapy affecting drug metabolism, pharmacokinetics, anti-tumor effects and toxicity. In conclusion, breast harbors a community of microbes that can communicate with the host cells inducing downstream signaling pathways and modulating various aspects of breast cancer growth and metastatic progression and an improved understanding of microbial dysbiosis can potentially reduce breast cancer risk and improve outcomes of breast cancer patients.The human microbiome, now referred to as, the “forgotten organ” contains a metagenome that is 100-fold more diverse compared to the human genome, thereby, is critically associated with human health [1,2]. With the revelations of the human microbiome project and advent of deep sequencing techniques, a plethora of information has been acquired in recent years. Body sites like stomach, bladder and lungs, once thought to be sterile, are now known to harbor millions of indigenous microbial species. Approximately 80% of the healthy microbiome consists of Firmicutes and Bacteroidetes accompanied by Verrucomicrobia, Actinobacteria, Proteobacteria, Tenericutes and Cyanobacteria [[2], [3], [4], [5], [6], [7]]. The role of microbiome in diabetes, obesity and even neurodegenerative diseases was greatly appreciated in the last decade [1,[7], [8], [9], [10], [11], [12], [13], [14]] and now it has been established that microbiome significantly contributes to many organ specific cancers [1,15,16].     

An approach to a physico-chemical model of olfactory stimulation in vertebrates by single compounds

During recent years, numerous attempts have been made to correlate both quantitative (Davies &; Taylor, 1959; Engen, 1962; Beck, 1964; Engen, Cain &; Rovee, 1968; Cain, 1969; Dravnieks &; Laffoit, 1970; Laffort, 1969a,b) and qualitative (Davies, 1965; Amoore &; Venstrom, 1965; Döving, 1966a,b; Wright &; Michels, 1964; Leveteau &; MacLeod, 1969) odorous properties of single compounds to their molecular properties. These attempts have been only partially successful.In the present paper we will try to explain the several odorous properties of single compounds on the basis of the non-specific properties of odorants involved in solubility.This model is a first approach, and although it gives statistically highly significant relations, it is not as accurate as those advanced with respect to the physical and sensory dimensions of stimuli in the fields of vision and audition.We will first give the present definitions of the most suitable physicochemical parameters, and then advance quantitative and qualitative models for single compounds. Quantitative odorous properties are: odour threshold, rate of change of odour intensity with odorant concentration in the suprathreshold region, and the somewhat controversial upper odour intensity. Qualitative properties refer to odour character.     

Non-linear regression of biological temperature-dependent rate models based on absolute reaction-rate theory

Biological temperature-dependent rate models based on Arrhenius' and Eyring's equations have been formulated by Johnson & Lewin (1946), Hultin (1955), and Sharpe & DeMichele (1977). The original formulation of Sharpe and DeMichele is poorly suited for non-linear regression. Very high correlations of parameter estimators occassionally make regression with their equation impossible using Marquardt's algorithm (1963).This analysis describes a new formulation of Sharpe and DeMichele's model that greatly alleviates the non-linear regression problem. It is partly based on Hultin's formulation (1955). Biological and graphical interpretation of the model parameters is discussed. Regression suitability is illustrated with a typical data set. Similar modifications to the equations of Hultin (1955) and Johnson & Lewin (1946) are described.     

The role of migration in the genetic structure of populations in temporally and spatially varying environments II. Island Models

The Island Model introduced by Sewall Wright (1951) has proven to be a useful construction for studying the interaction of genetic drift, population subdivision, and mutation. Interest in the model has recently increased because of its relevance to certain questions involving the rate of differentiation of sub-populations under the neutral allele hypothesis (e.g., Smith, 1970; Latter, 1973). It is perhaps the only realistic population structure in which the test for neutrality proposed by Lewontin and Krakauer (1973) is valid (Lewontin and Krakauer, 1975). If data from natural populations is to be compared to the predictions of the Island Model, it is desirable to have an alternative model with the same migration pattern but with natural selection operating. In this paper one such model will be introduced where the stochastic element comes from random fluctuations in the environment rather than from genetic drift. The model is a direct extension of the one in the previous paper in this series (Gillespie, 1975) which dealt with a population which is subdivided into two patches with restricted migration between them.     

Kinship and covariance

Price's (1970) covariance theorem can be used to derive an expression for gene frequency change in kin selection models in which the fitness effect of an act is independent of the genotype of the recipient. This expression defines a coefficient of relatedness which subsumes r(Wright, 1922), b(Hamilton, 1972), ρ (Orlove &; Wood, 1978), and R(Michod &; Hamilton, 1980). The new coefficient extends the domain of Hamilton's rule to models in which the average gene frequency of actors differs from that of recipients.     

Nouvelles observations de cannelures horizontalessur les berges vaseuses de l'estuaire de la Gambie et leur interpretation comme traces de broutage de poissons

Localisation, morphology and scratches wich characterise fluting features observed in the Gambia estuary are due 0610 to the feeding activity of fishes (as have suggested Schwarz et alii, 1975) and not due to the effects of biodestruction as proposed by F. Teissier (1957).     

A new genus Thubdora Park,gen. nov. and seven new species of the subfamily Torodorinae (Lepidoptera,Lecithoceridae) from Cameroon and Rep. of Congo,Africa

Based on the material collected from Cameroon in 1913–1918 and Congo in 1993 which are preserved in the Carnegie Museum of Natural History, Pittsburgh, USA, a new genus Thubdora Park, gen. nov. and seven new species of the subfamily Torodorinae (Lecithoceridae) are described. They are Torodora efulenensis sp. nov., Dragmatucha hispidula sp. nov.; and five species of Thubdora: T. acutalis sp. nov., T. bilobella sp. nov., T. aciphalla sp. nov., T. ambliodes sp. nov., and T. cameroona sp. nov. In addition, six species of Lecithocera Herrich-Shäffer described by Viette, 1955, Viette, 1986 and Meyrick, 1931, Meyrick, 1933 are newly transferred to Torodora and its related genera, due to the male genital characters: Idiopteryx adella (Viette, 1955), comb. nov.; Thubdora decavella (Viette, 1955), comb. nov.; Thubdora mocquerysella (Viette, 1955), comb. nov.; Torodora kambanella (Viette, 1986), comb. nov.; Torodora masoalella (Viette, 1955), comb. nov.; Torodora monobyrsa (Meyrick, 1931), comb. nov.; and T. ochrometra (Meyrick, 1933), comb. nov. For the new species, images of adults with their labels and genitalia are provided.     

Structure d'adhérencedes grains de pollen en tétrade du genre Classopollis PFLUG, 1953, de l'Hettangien de Saint-Fromont,Manche (France)

Palynological inventory of Saint-Fromont pit 0815 (Manche, France) related to Hettangian seems to show the conspecificity of Classopollis chateaunoviReyre, 1970, Classopollis kieseriReyre, 1970 and Classopollis harisiiMuir & Van Konijnenburg-Van Cittert, 1970. SEM pictures exibit some sculptural elements interpreted as structural attachments of grains in tetrad and compared to those of genus DicheiropollisTrevisan, 1971.     

Révision d'?Orthis? berthoisiRouault, 1849Orthida (Brachiopoda) de l'Ordovicien du Massif Armoricain

Since it is impossible to state about any genericassignment for Orthis berthoisiRouault, 1849the species name is herein restricted to original specimens figured by the author. The study of the Brachiopods from the St-Germain-sur-Ille Formation allows to confirm the first determination by De Tromelin &Lebesconte (1875)and to establish their conspecificity with Orthis berthoisi var. erratica described in 1869 by Davidson from the Budleigh-Salterton pebbles. The successive assignment of the species erratica to the genus Svobodaina(Cocks, 1978) then to Corineorthis(Cocks & Lockley, 1981) is discussed. The attribution to the genus DrabovinellaHavlicek, 1951appears most likely.     

Fluorocitrate inhibition of aconitase. Reversibility of the inactivation

Fluoride ion is released nearly stoichiometrically when (?)-erythro-fluorocitrate is incubated with aconitase. The release of F^? parallels the loss in activity and could arise from direct displacement of F^? by a base on the enzyme or from dehydration to fluoro-cis-aconitate and attack of an enzymic base to release F^?. Aconitase inactivated by ¹⁴C-fluorocitrate does not retain radioactivity when passed through G-50 Sephadex or precipitated by ammonium sulfate. Fullenzymicactivity can be regained after either of these treatments by activation by cysteine and ferrous salts. These data are consistent with the report of fluorocitrate being a competitive (and non-competitive) inhibitor of aconitase (Villafranca, J.J. (1972) Intra-Science Chem. Rept. 6 (4), 1–11) which rapidly inactivates the enzyme. This inactivated enzyme may be a very labile covalent complex, a very tight complex between enzyme and fluoro-cis-aconitate or a tight complex between a defluorinated deravitive of fluorocitrate.In the course of Peters (1957) extensive work on the toxic effects of fluoroacetate, he determined that fluoroacetate was metabolically converted to fluorocitrate. This finding and the fact that citrate levels rise soon after ingestion of fluoroacetate led to the suggestion that fluorocitrate inactivates aconitase (E.C. 4.2.1.2).Recently, conflicting reports concerning the site of inactivation in mitochondria by the inhibiting isomer of fluorocitrate, (?)-erythro-fluorocitrate (1R:2R, 1-fluoro-2-hydroxy-1,2,3-propanetricarboxylate) have appeared (Eanes et al. 1972; Brand et al, 1973). Eanes et al. (1972) contends that the tricarboxylate carrier is the site of inhibition, while Brand et al. (1973) has compelling evidence that aconitase is the site of inhibition. This controversy is a matter of intrepretation of the results and a greater knowledge of the inactivation of aconitase by fluorocitrate may be useful in these interpretations. The results reported herein are concerned with the mechanism of inactivation of purified mitochondrial aconitase by fluorocitrate and demonstrate that this reaction is readily reversible.     

Revision of citrus trees pests of Agrilus angulatus species–group (Coleoptera,Buprestidae) from South and Southeast Asia with description of one new species

The revision of Agrilus (Coleoptera, Buprestidae) pests of citrus trees from A. angulatus species–group comprising six species: A. angulatus (Fabricius, 1798); A. connatus sp. nov.; A. livensKerremans, 1892a, Kerremans, 1892b; A. mediocrisKerremans, 1900; A. nubilusKerremans, 1892a, Kerremans, 1892b and A. olivaceidorsisObenberger, 1917 from South and Southeast Asia is provided. The study is based on examination of all relevant types and 2498 additional specimens. The key to species is given and complemented with illustrations of morphology, habitus, genitalia, size variability, color variability, type specimens and distribution. Comprehensive commented literature references, data on type specimens, faunal records, revised and updated distribution and host plant data are cited for each species. The new species A. connatus sp. nov. from Laos and Thailand is described. The following taxonomic and nomenclatural acts are proposed: the name grisatorKerremans, 1893syn. nov. (Agrilus) is a junior subjective synonym of the name nubilusKerremans, 1892a, Kerremans, 1892b (Agrilus); the name macellusBourgoin, 1922syn. nov. (Agrilus) is a junior subjective synonym of the name olivaceidorsisObenberger, 1917 (Agrilus); the lectotype of Buprestis angulataFabricius, 1798 (now in Agrilus) is designated.www.zoobank.org/urn:lsid:zoobank.org:pub:BAE5BD51-2811-44CE-8BC1-AEEC76075667     

A mechanism for the hydrolysis of MgATP by actomyosin of skeletal muscle.

Based on a model of the active site of myosin (Ramirez, Shukla &; Levy, 1978), a chemical mechanism for MgATPase and intermediate oxygen exchange is presented. In this mechanism, oxygen exchange takes place via an oxyphosphorane intermediate that undergoes double turnstile rotation (Ugi, Ramirez, Marquarding, Klusacek &; Gillespie, 1971; Ramirez &; Ugi, 1974. During hydrolysis by native skeletal muscle myosin, only three [¹⁸O] atoms from labelled water are rapidly incorporated into the phosphorus that is finally released to the medium as P_i; whereas, during hydrolysis by subfragment 1 (S1), which is the head of myosin, four oxygens are labelled rapidly. To explain this difference, we postulate that cleavage of the (S1)-(S2) hinge in the preparation of S1 modifies the interaction of the oxyphosphorane intermediate at the active site. This enables a normally non-exchangeable oxygen to enter the exchange process. This is consistent with our earlier interpretation to the effect that the active site and the hinge in myosin are relatively close to each other Shukla &; Levy, 1977b; Shukla &; Levy, 1978. We postulate that the major elements of the active site are situated on a 92 amino acid fragment, p₁₀, isolated by Elzinga &; Collins, 1977 from myosin. P₁₀ is now known to be situated in the region that connects the head to the body of a myosin heavy chain (Lu, Sosinki, Balint &; Streter, 1978). An examination of the p₁₀ fragment for a possible point of proteolytic attack in the region of the hinge which will generate S1 revealed lysine 82. Breaking the protein chain at a point so close to the active site pocket could explain the effect of hinge cleavage on oxygen exchange. Two additional features of the present mechanism are: (1) the protonation of P_γ of a MgP_α,P_γ complex of ATP, which depresses monomeric metaphosphate mediated hydrolysis, and enhances oxyphosphorane formation by addition of water to P_γ; (2) the coordination of N^τ-methylhistidinet² of actin with Mg at the active site, which activates the release of the products of hydrolysis.     

Box-Jenkins forecasting in ecology: An answer to poole

This answering of Poole, 1978, Poole, 1976 aims at rounding off our exchange of views, without losing the readership from an excess of toing and froing between the four contributions. So my final rejoinder only attempts at treating the general points raised by Poole (1978), rather than taking issue with all the minutiae, which would require too many quotes of quotes and counterquotes. The main nub of contention remains as to whether or not statistical fits can be meaningfully interpreted biologically.     

The fine structure of Ameson pulvis (Microspora,Microsporida) and its implications regarding classification and chromosome cycle

Nosema pulvisPerez, 1905, Ameson pulvis (Perez) Sprague, 1977, in muscles of the crabs Carcinus maenas and C. mediterraneus from the coast of France, was observed with the electron microscope. It was found to be structurally similar to the type species A. michaelis (Sprague, 1970). Sprague, 1977, having moniliform sporogonial plasmodia, unikaryotic sporoblasts, and hirsute sporulation stages. It is treated as distinct from A. michaelis because it has slightly smaller spores (by comparison with syntype material of A. michaelis) and appears to have fewer coils in the polar filament. The results require the removal of the genus Ameson from the family Nosematidae Labbé, 1899, where Sprague (1977) had placed it under the erroneous supposition that its sporoblasts are diplokaryotic. Ameson is transferred to family Unikaryonidae Sprague, 1977. Ameson is distinguished from PereziaLéger and Duboscq, 1909, shown by Ormieres et al. to have a similar developmental pattern, by presence of appendages on its sporulation stage. A. nelsoni (Sprague, 1950), the third, and only other species of Ameson, lacks the appendages and is transferred to genus Perezia.     

Does a functional relationship exist between the polymerization and catalytic activity of beef liver glutamate dehydrogenase?

The recent work of Cohen &; Benedek (1976) and Cohen et al. (1975, 1976) on the apparent interdependence of beef liver glutamate dohydrogenase catalytic activity and degree of polymerization is examined in the light of previously published equilibrium and kinetic results. It is shown that some of the hypotheses central to the Cohen &; Benedek (1976) model are in contradiction with existent data. Consideration of all available information leads to the conclusion that effector-induced depolymerization may simply be an incidental side reaction in the events leading to inhibition.     

An autoradiographic analysis of the time of appearance of neurons in the developing chick neural retina

The pattern of incorporation of [³H]thymidine into the chick neural retina has been used to establish the time and order in which different classes of neuroepithelial cells withdraw from the cell cycle and initiate migration and differentiation.The posterior pole of the retina is the first to form during development. In this region most neuroepithelial cells complete mitotic activity between the third and sixth day of incubation. Presumptive ganglion cells initiate the withdrawal process, and they are soon followed by the neuroepithelial precursors of amacrine, horizontal, and receptor cells. Bipolar cell precursors are the last to begin and the last to complete cell cycle activity. It is worthy of note, however, that, in any given region of the retina, neuroepithelial cells of all types cease mitosis in close, overlapping succession.These results are in reasonable agreement with those previously published on the chick retina by Fujita and Horii (1963), and other investigators on the mouse (Mus), killifish (Fundulus), and toad (Xenopus). The present data are also consistent with those proposals of Angevine (1970), Jacobson, 1968a, Jacobson, 1968b, Jacobson, 1970, and others that relate the cessation of mitotic activity of neuroepithelial cells to the determination of neuronal size, axon length, and the specification of neuronal connections.