Cardiovascular, Antinociceptive and Sedative Effects of Medetomidine Infusion in Sevoflurane Anesthesia in Puppies

The objective of this study was to determine the effect of a constant rate infusion of medetomidine in the cortical brain activity and hemodynamic parameters in sevoflurane anesthetized puppies. Six puppies of the age of two weeks old were included in the study and were anaesthetized three times with sevoflurane. On the first anesthesia, each dog’s minimum alveolar concentration (MAC) for sevoflurane was determined by the use of the tail clamp method. On the second anesthesia (sevoflurane), the puppies were anesthetized at each of five multiples of their individual’s MAC, 0.75, 1, 1.25, 1.5 and 1.75 MAC, and bispectral index and cardiorespiratory parameters were registered. On the third anesthesia (sevoflurane+ medetomidine), puppies were anesthetized at each of five multiples of their individual’s MAC, and medetomidine (5 µg/kg+2µg/kg/h) was administered. Mild cardiovascular depression was observed in sevoflurane+medetomidine in comparison with sevoflurane. Cortical and antinociceptive effects were not observed with medetomidine infusion although a mature EEG response to noxious stimulation would not have developed in puppies. Central alpha-2 adrenoreceptors would be immature in puppies during the first two weeks of life, and for this reason, medetomidine would not produce sedative and analgesic effects in young puppies. More studies have to be performed to support this statement

Quantitative study of hydration of C3S and C2S by thermal analysis. Evolution and composition of C-S-H gels formed

This research is part of a European project (namely, CODICE project), main objective of which is modelling, at a multi-scale, the evolution of the mechanical performance of non-degraded and degraded cementitious matrices. For that, a series of experiments were planned with pure synthetic tri-calcium silicate (C3S) and bi-calcium silicate (C2S) (main components of the Portland cement clinker) to obtain different calcium–silicate–hydrate (C–S–H) gel structures during their hydration. The characterization of those C–S–H gels and matrices will provide experimental parameters for the validation of the multi-scale modelling scheme proposed. In this article, a quantitative method, based on thermal analyses, has been used for the determination of the chemical composition of the C–S–H gel together with the degree of hydration and quantitative evolution of all the components of the pastes. Besides, the microstructure and type of silicate tetrahedron and mean chain length (MCL) were studied by scanning electron microscopy (SEM) and 29Si magic-angle-spinning (MAS) NMR, respectively. The main results showed that the chemical compositions for the C–S–H gels have a CaO/SiO2 M ratio almost constant of 1.7 for both C3S and C2S compounds. Small differences were found in the gel water content: the H2O/SiO2 M ratio ranged from 2.9 ± 0.2 to 2.6 ± 0.2 for the C3S (decrease) and from 2.4 ± 0.2 to 3.2 ± 0.2 for the C2S (increase). The MCL values of the C–S–H gels, determined from 29Si MAS NMR, were 3.5 and 4 silicate tetrahedron, for the hydrated C3S and C2S, respectively, remaining almost constant at all hydration periods

Influences of Excluded Volume of Molecules on Signaling Processes on Biomembrane

We investigate the influences of the excluded volume of molecules on biochemical reaction processes on 2-dimensional surfaces using a model of signal transduction processes on biomembranes. We perform simulations of the 2-dimensional cell-based model, which describes the reactions and diffusion of the receptors, signaling proteins, target proteins, and crowders on the cell membrane. The signaling proteins are activated by receptors, and these activated signaling proteins activate target proteins that bind autonomously from the cytoplasm to the membrane, and unbind from the membrane if activated. If the target proteins bind frequently, the volume fraction of molecules on the membrane becomes so large that the excluded volume of the molecules for the reaction and diffusion dynamics cannot be negligible. We find that such excluded volume effects of the molecules induce non-trivial variations of the signal flow, defined as the activation frequency of target proteins, as follows. With an increase in the binding rate of target proteins, the signal flow varies by i) monotonically increasing; ii) increasing then decreasing in a bell-shaped curve; or iii) increasing, decreasing, then increasing in an S-shaped curve. We further demonstrate that the excluded volume of molecules influences the hierarchical molecular distributions throughout the reaction processes. In particular, when the system exhibits a large signal flow, the signaling proteins tend to surround the receptors to form receptor-signaling protein clusters, and the target proteins tend to become distributed around such clusters. To explain these phenomena, we analyze the stochastic model of the local motions of molecules around the receptor.Comment: 31 pages, 10 figure

Direct glia-to-neuron transdifferentiation gives rise to a pair of male-specific neurons that ensure nimble male mating

Sexually dimorphic behaviours require underlying differences in the nervous system between males and females. The extent to which nervous systems are sexually dimorphic and the cellular and molecular mechanisms that regulate these differences are only beginning to be understood. We reveal here a novel mechanism by which male-specific neurons are generated in Caenorhabditis elegans through the direct transdifferentiation of sex-shared glial cells. This glia-to-neuron cell fate switch occurs during male sexual maturation under the cell-autonomous control of the sex-determination pathway. We show that the neurons generated are cholinergic, peptidergic, and ciliated putative proprioceptors which integrate into male-specific circuits for copulation. These neurons ensure coordinated backward movement along the mate’s body during mating. One step of the mating sequence regulated by these neurons is an alternative readjustment movement performed when intromission becomes difficult to achieve. Our findings reveal programmed transdifferentiation as a developmental mechanism underlying flexibility in innate behaviour

Cryo-EM structure of a helicase loading intermediate containing ORC-Cdc6-Cdt1-MCM2-7 bound to DNA

In eukaryotes, the Cdt1-bound replicative helicase core MCM2-7 is loaded onto DNA by the ORC-Cdc6 ATPase to form a prereplicative complex (pre-RC) with an MCM2-7 double hexamer encircling DNA. Using purified components in the presence of ATP-γS, we have captured in vitro an intermediate in pre-RC assembly that contains a complex between the ORC-Cdc6 and Cdt1-MCM2-7 heteroheptamers called the OCCM. Cryo-EM studies of this 14-subunit complex reveal that the two separate heptameric complexes are engaged extensively, with the ORC-Cdc6 N-terminal AAA+ domains latching onto the C-terminal AAA+ motor domains of the MCM2-7 hexamer. The conformation of ORC-Cdc6 undergoes a concerted change into a right-handed spiral with helical symmetry that is identical to that of the DNA double helix. The resulting ORC-Cdc6 helicase loader shows a notable structural similarity to the replication factor C clamp loader, suggesting a conserved mechanism of action

New ophthalmosaurid ichthyosaurs from the European lower cretaceous demonstrate extensive ichthyosaur survival across the Jurassic–Cretaceous boundary

Background Ichthyosauria is a diverse clade of marine amniotes that spanned most of the Mesozoic. Until recently, most authors interpreted the fossil record as showing that three major extinction events affected this group during its history: one during the latest Triassic, one at the Jurassic–Cretaceous boundary (JCB), and one (resulting in total extinction) at the Cenomanian-Turonian boundary. The JCB was believed to eradicate most of the peculiar morphotypes found in the Late Jurassic, in favor of apparently less specialized forms in the Cretaceous. However, the record of ichthyosaurs from the Berriasian–Barremian interval is extremely limited, and the effects of the end-Jurassic extinction event on ichthyosaurs remains poorly understood. Methodology/Principal Findings Based on new material from the Hauterivian of England and Germany and on abundant material from the Cambridge Greensand Formation, we name a new ophthalmosaurid, Acamptonectes densus gen. et sp. nov. This taxon shares numerous features with Ophthalmosaurus, a genus now restricted to the Callovian–Berriasian interval. Our phylogenetic analysis indicates that Ophthalmosauridae diverged early in its history into two markedly distinct clades, Ophthalmosaurinae and Platypterygiinae, both of which cross the JCB and persist to the late Albian at least. To evaluate the effect of the JCB extinction event on ichthyosaurs, we calculated cladogenesis, extinction, and survival rates for each stage of the Oxfordian–Barremian interval, under different scenarios. The extinction rate during the JCB never surpasses the background extinction rate for the Oxfordian–Barremian interval and the JCB records one of the highest survival rates of the interval. Conclusions/Significance There is currently no evidence that ichthyosaurs were affected by the JCB extinction event, in contrast to many other marine groups. Ophthalmosaurid ichthyosaurs remained diverse from their rapid radiation in the Middle Jurassic to their total extinction at the beginning of the Late Cretaceous

Land of Addicts? An Empirical Investigation of Habit-Based Asset Pricing Models

A popular explanation of aggregate stock market behavior suggests that assets are priced as if there were a representative investor whose utility is a power function of the difference between aggregate consumption and a “habit” level, where the habit is some function of lagged and (possibly) contemporaneous consumption. But theory does not provide precise guidelines about the parametric functional relationship between the habit and aggregate consumption. This makes for- mal estimation and testing challenging; at the same time, it raises an empirical question about the functional form of the habit that best explains asset pricing data. This paper studies the ability of a general class of habit-based asset pricing models to match the conditional moment restrictions implied by asset pricing theory. Our approach is to treat the functional form of the habit as unknown, and to estimate it along with the rest of the model’s finite dimensional parameters. This semiparametric approach allows us to empirically evaluate a number of interesting hypotheses about the specification of habit-based asset pricing models. Using stationary quarterly data on consumption growth, assets returns and instruments, our empirical results indicate that the estimated habit function is nonlinear, the habit formation is internal, and the estimated time-preference parameter and the power utility parameter are sensible. In addition, our estimated habit function generates a positive stochastic discount factor (SDF) proxy and performs well in explaining cross-sectional stock return data. We find that an internal habit SDF proxy can explain a cross-section of size and book-market sorted portfolio equity returns better than (i) the Fama and French (1993) three-factor model, (ii) the Lettau and Ludvigson (2001b) scaled consumption CAPM model, (iii) an external habit SDF proxy, (iv) the classic CAPM, and (v) the classic consumption CAPM

The granite‑hosted Variscan gold deposit from Santo António mine in the Iberian Massif (Penedono, NW Portugal): constraints from mineral chemistry, fuid inclusions, sulfur and noble gases isotopes

The study area is located in the Central Iberian Zone, a major tectonic unit of the Iberian Massif (Variscan belt). In this region the basement is composed of Cambrian-Ordovician sedimentary and minor volcanic rocks that underwent deformation and metamorphism during the Carboniferous. These metamorphic rocks host ca. 331–308 Ma granitic plutons emplaced during the D2 extensional and D3–D4 contractional deformation phases. The gold-bearing quartz veins from the Santo António mine (Penedono region) occur in granite formed at 310.1 ± 1.1 Ma and post-dated the peak of metamorphism. Gold–silver alloy is included in quartz, but mainly occurs in spaces between grains or micro-fractures within arsenopyrite of all three generations and less in pyrite. Late sulphides and sulphosalts were deposited along fractures mainly in arsenopyrite, and locally surrounding the gold–silver alloy grains. Ferberite, scheelite and stolzite replace arsenopyrite. The abundant aqueous carbonic fluids and the occurrence of a low-salinity fluid and their minimum possible entrapment temperature of 360–380 °C suggest that this gold-forming event began during the waning stages of the Variscan orogeny. The mean δ34S values of arsenopyrite and pyrite are − 4.7‰ and − 3.8‰, respectively. He–Ar–Ne isotopic data suggest a crustal origin. The ascent of the granite magma has provided the heat for remobilization of gold, other metals and metalloids from the metamorphic rocks. This gold-arsenopyrite deposit has thus similar characteristics as other selected gold-arsenopyrite deposits from the Iberian Massif, but it contains tungstates.El área de estudio está ubicada en la Zona Centroibérica, una importante unidad tectónica del Macizo Ibérico (cinturón varisco). En esta región el basamento está compuesto por rocas sedimentarias y volcánicas del Cámbrico-Ordovícico tectonizadas y metamorfzadas durante el Carbonífero. Estas rocas metamórfcas sirven como caja de los plutones graníticos datados en torno a 331–308 Ma y que fueron emplazados durante la fase de deformación extensional D2 y las fases de deformación contraccional D3 y D4. Las venas de cuarzo ricas en oro de la mina de Santo António (región de Penedono) que aparecen en un granito datado a los 310.1 ± 1.1 Ma son posteriores al pico metamórfco regional. La aleación de oro y plata se incluye en el cuarzo, pero se produce principalmente en los espacios entre granos o micro-fracturas dentro de arsenopirita de las tres generaciones y menos en pirita. Los sulfuros y sulfuros tardíos se depositaron a lo largo de las fracturas principalmente en arsenopirita, y alrededor de los granos de aleación de oro y plata. Ferberita, scheelita y la estolzita sustituyen a la arsenopirita. Los abundantes líquidos acuosos carbónicos y la presencia de un fuido de baja salinidad y su posible temperatura de atrapamiento mínima en torno de 360-380 ºC sugieren que este evento de formación de oro comenzó durante las etapas fnales de la orogenia varisca. Los valores medios de S de arsenopirita y pirita son − 4.7 ‰ y − 3.8 ‰, respectivamente. Los datos isotópicos de He–Ar–Ne sugieren que en el origen de los fuidos mineralizados participa la corteza continental. El ascenso del magma granítico ha provisto el calor para la movilización del oro, otros metales y metaloides desde las rocas metamórfcas. Este depósito de oroarsenopirita tiene así características similares a otros yaciamientos con arsenopirita y oro del Macizo Ibérico, pero sin embargo contienen tungstates.This research was financially supported by Fundação para a Ciência e Tecnologia through the projects GOLDGranites, Orogenesis, Long-term strain/stress and Deposition of ore metals—PTDC/GEO-GEO/2446/2012: COMPETE: FCOMP-01-0124-FEDER-029192 and UID/GEO/04035/2013

PCB pollution continues to impact populations of orcas and other dolphins in European waters

Organochlorine (OC) pesticides and the more persistent polychlorinated biphenyls (PCBs) have well-established dose-dependent toxicities to birds, fish and mammals in experimental studies, but the actual impact of OC pollutants on European marine top predators remains unknown. Here we show that several cetacean species have very high mean blubber PCB concentrations likely to cause population declines and suppress population recovery. In a large pan-European meta-analysis of stranded (n = 929) or biopsied (n = 152) cetaceans, three out of four species:- striped dolphins (SDs), bottlenose dolphins (BNDs) and killer whales (KWs) had mean PCB levels that markedly exceeded all known marine mammal PCB toxicity thresholds. Some locations (e.g. western Mediterranean Sea, south-west Iberian Peninsula) are global PCB "hotspots" for marine mammals. Blubber PCB concentrations initially declined following a mid-1980s EU ban, but have since stabilised in UK harbour porpoises and SDs in the western Mediterranean Sea. Some small or declining populations of BNDs and KWs in the NE Atlantic were associated with low recruitment, consistent with PCB-induced reproductive toxicity. Despite regulations and mitigation measures to reduce PCB pollution, their biomagnification in marine food webs continues to cause severe impacts among cetacean top predators in European seas