Absolute configuration and conformation of the pure opioid antagonist (+)-2,9 alpha-dimethyl-5-(m-hydroxyphenyl)morphan.

(+)-2,9 alpha-Dimethyl-5-(m-hydroxyphenyl)morphan is the only phenylmorphan analog whose affinity for opioid kappa-receptors is greater than its affinity for opioid mu-receptors. Pharmacologically, the compound is a pure opioid antagonist devoid of agonist activity in in vivo assays of antinociception. The absolute configuration of the compound has been determined to be (1R,5S,9R) from an X-ray crystallographic study of the chloride salt. Thus, the absolute configuration corresponds to that of the atypical opioid agonist (-)-phenylmorphan while the weak atypical agonist (-)-2,9 alpha-dimethyl-5-(m- hydroxyphenyl)morphan corresponds to the potent morphine-like (+)-phenylmorphan. The preferred orientations of the phenyl ring for the two stereoisomers were determined using the molecular mechanics program MM2-87 and found to vary from that of the two parent compounds. The atypical properties of the two 9 alpha-methyl analogs is consistent with an opioid ligand model which proposes that morphine-like properties require a particular range of phenyl orientations. There was good agreement between the structure obtained from X-ray crystallography and computed with the MM2-87 program.     

Interacting forces of predation and fishing affect species’ maturation size

1. Fishing is a strong selective force and is supposed to select for earlier maturation at smaller body size. However, the extent to which fishing‐induced evolution is shaping ecosystems remains debated. This is in part because it is challenging to disentangle fishing from other selective forces (e.g., size‐structured predation and cannibalism) in complex ecosystems undergoing rapid change.
2. Changes in maturation size from fishing and predation have previously been explored with multi‐species physiologically structured models but assumed separation of ecological and evolutionary timescales. To assess the eco‐evolutionary impact of fishing and predation at the same timescale, we developed a stochastic physiologically size‐structured food‐web model, where new phenotypes are introduced randomly through time enabling dynamic simulation of species'' relative maturation sizes under different types of selection pressures.
3. Using the model, we carried out a fully factorial in silico experiment to assess how maturation size would change in the absence and presence of both fishing and predation (including cannibalism). We carried out ten replicate stochastic simulations exposed to all combinations of fishing and predation in a model community of nine interacting fish species ranging in their maximum sizes from 10 g to 100 kg. We visualized and statistically analyzed the results using linear models.
4. The effects of fishing on maturation size depended on whether or not predation was enabled and differed substantially across species. Fishing consistently reduced the maturation sizes of two largest species whether or not predation was enabled and this decrease was seen even at low fishing intensities (F = 0.2 per year). In contrast, the maturation sizes of the three smallest species evolved to become smaller through time but this happened regardless of the levels of predation or fishing. For the four medium‐size species, the effect of fishing was highly variable with more species showing significant and larger fishing effects in the presence of predation.
5. Ultimately our results suggest that the interactive effects of predation and fishing can have marked effects on species'' maturation sizes, but that, at least for the largest species, predation does not counterbalance the evolutionary effect of fishing. Our model also produced relative maturation sizes that are broadly consistent with empirical estimates for many fish species.

     

TRIM32/USP11 Balances ARID1A Stability and the Oncogenic/Tumor-Suppressive Status of Squamous Cell Carcinoma

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An active balance board system with real-time control of stiffness and time-delay to assess mechanisms of postural stability

Increased time-delay in the neuromuscular system caused by neurological disorders, concussions, or advancing age is an important factor contributing to balance loss (Chagdes et al., 2013, 2016a,b). We present the design and fabrication of an active balance board system that allows for a systematic study of stiffness and time-delay induced instabilities in standing posture. Although current commercial balance boards allow for variable stiffness, they do not allow for manipulation of time-delay. Having two controllable parameters can more accurately determine the cause of balance deficiencies, and allows us to induce instabilities even in healthy populations. An inverted pendulum model of human posture on such an active balance board predicts that reduced board rotational stiffness destabilizes upright posture through board tipping, and limit cycle oscillations about the upright position emerge as feedback time-delay is increased. We validate these two mechanisms of instability on the designed balance board, showing that rotational stiffness and board time-delay induced the predicted postural instabilities in healthy, young adults. Although current commercial balance boards utilize control of rotational stiffness, real-time control of both stiffness and time-delay on an active balance board is a novel and innovative manipulation to reveal balance deficiencies and potentially improve individualized balance training by targeting multiple dimensions contributing to standing balance.     

Salt marsh harvest mouse demography and habitat use in the Suisun Marsh,California

We undertook a 2-year (2002–2004) mark–recapture study to investigate demographic performance and habitat use of salt marsh harvest mice (Reithrodontomys raviventris halicoetes) in the Suisun Marsh. We examined the effects of different wetland types and microhabitats on 3 demographic variables: density, reproductive potential, and persistence. Our results indicate that microhabitats dominated by mixed vegetation or pickleweed (Salicornia spp.) supported similar salt marsh harvest mouse densities, reproductive potential, and persistence throughout much of the year, whereas few salt marsh harvest mice inhabited upland grass-dominated microhabitats. We found that densities were higher in diked wetlands, whereas post-winter persistence was higher in tidal wetlands, and reproductive potential did not differ statistically between wetland types. Our results emphasize the importance of mixed vegetation for providing adequate salt marsh harvest mouse habitat and suggest that, despite their physiognomic and hydrological differences, both diked and tidal wetlands support salt marsh harvest mouse populations by promoting different demographic attributes. We recommend that habitat management, restoration, and enhancement efforts include areas containing mixed vegetation in addition to pickleweed in both diked and tidal wetlands. © 2011 The Wildlife Society.     

On the choice of the optimal periodic operation for a continuous fermentation process

In this contribution we investigate the impact of the forcing waveform on the productivity of a continuous bioreactor governed by an unstructured, nonlinear kinetic model. The (periodic) forcing is applied on the substrate concentration in the feed. To this end, some alternative waveforms commonly encountered in practice are evaluated and their performance is compared. An analytical/numerical approach is used. The preliminary analytical step is based on the π‐criterion that gives useful information for small amplitudes. The extension to larger amplitudes, when significant improvements are expected, is then performed through a continuation‐optimization procedure. It is found that the choice of the specific waveform has an impact on the performance of the process and there is no unique best forcing for any process condition, but its choice depends on the operating parameters and the forcing amplitude and frequency values. Further, the influence of the waveform functions on the wash‐out conditions are extensively examined. The analysis shows that all the waveforms examined in this work may lead to significant enlargement of the nontrivial regime with respect to a steady state operation. In particular, square‐wave forcing leads in practice to the extinction of the wash‐out conditions for any feed substrate concentration and for a well defined choice of the forcing parameters. © 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2010     

Early changes in mitochondrial monoamine oxidase activity of rat liver during 2-acetylaminofluorene feeding

The activities of mitochondrial type A and B monoamine oxidase were determined in the liver of rats fed a diet containing 2-acetylaminofluorene (AAF). Three days after the initiation of AAF-feeding, there was a significant decrease of type B monoamine oxidase activity without affect on type A enzyme. The decreased activity of type B monoamine oxidase, which reached a minimum after three weeks, was sustained for as long as AAF-feeding was continued. Sex-related difference in response to AAF was seen in the rat with respect to the onset and the intensity of the decreased type B monoamine oxidase activity, male rats being more sensitive to the carcinogen than female rats. In contrast to the in vivo effect, AAF showed a potent inhibitory effect on type A monoamine oxidase, rather than on type B enzyme, when added in vitro. The pI₅₀ values were estimated to be 7.5 against type A monoamine oxidase and 4.1 against type B enzyme, respectively. The in vitro inhibition of both types of monoamine oxidase by AAF was competitive. The K_i values for AAF were calculated to be 9.51 · 10^?9 M for type A monoamine oxidase and 1.30 · 10^?5 M for type B enzyme, respectively. In accordance with the potent inhibitory effect of AAF on type A monoamine oxidase in vitro, a single administration of the carcinogen, at a dose of 50 mg/kg, resulted in a marked and temporal decrease of the enzyme activity in the mitochondria of male rat liver. Recovery of the decreased type B monoamine oxidase activity was slow, and the enzyme activity did not return to control levels, even if rats were fed the basal diet for 2 or 4 weeks after the cessation of AAF-feeding.     

Feeding preference by the male blowfly Phormia regina for some natural foods and its relation to carbohydrate, amino acid, and alcohol content

The male blowfly, Phormia regina Meigen shows preference among a variety of natural and artificial foods. In a laboratory study preference was observed among sweet and fermenting juices as well as between liver and fish. The preferences between fresh and fermenting juices were based not only on component sugars, but also on other components, namely, amino acids, alcohol salts and presumably other chemical compounds. The preference between decaying liver and fish was probably based partly on the composition and concentration of amino acids in these foods. A variety of amino acids were found in foods and some of these amino acids were shown to be excitatory, some inhibitory and others neutral. Salts were also observed to be present in the juices; and in a laboratory study NaCl at lower concentrations acted synergestically with 0.1 M sucrose and at higher concentrations repulsive. It is suggested that feeding preference is based on several chemicals which behave either in an excitatory, additive, neutral, inhibitory or synergistic manner. The ratio of excitants to inhibitants is important in deciding the direction of preference.

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Résumé P. regina Meigen mâle préfere certains aliments naturels ou artificiels. Au laboratoire ses préférences parmi les jus sucrés sont les suivantes: orange > miel > pomme > sucrose 0.1 M; et parmi les aliments en décomposition: sucrose 0.1 M > foie > poisson. Les jus frais sont préférés aux jus fermentés. Les préférences ne dépendent pas seulement de la nature des sucres, mais aussi des acides aminés, de l'alcool, des sels et probablement d'autres substances chimiques. Le foie contient à la fois le plus grand nombre et la concentration la plus élevée en acides aminés, ce qui explique partiellement le goût pour le foie. Expérimentalement on peut classer les acides aminés en stimulants, inhibiteurs et neutres. Des sels ont été notés dans les jus, mais aucune analyse qualitative et quantitative n'en a été faite. Mélangé à du sucrose à 0.1 M, NaCl agit en synergie aux faibles concentrations, devient neutre à 0.175 M et à des concentrations supérieures le sucrose seul est préféré au mélange avec NaCl. Cependant, un mélange de NaCl à 0.25 M (bien qu'une telle concentration soit peu probable dans des jus végétaux) avec du sucrose à 0.1 M était préféré à l'eau. Il en est déduit que les préférences alimentaires. dans la nature sont orientées par plusieurs substances chimiques qui se comportent d'une façon stimulante, additive, neutre, inhibitrice ou synergique, et que les préférences alimentaires sont relatives. Le rapport de stimulants sur inhibiteurs est important dans la détermination du sens de la préférence.

     

Mitochondrial Oxidative Phosphorylation Complex Regulates NLRP3 Inflammasome Activation and Predicts Patient Survival in Nasopharyngeal Carcinoma

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Highlights

• •Flow cytometry analysis is used to isolate ASC speck⁽⁺⁾ NPC cells.
• •Proteome analysis of ASC speck⁽⁺⁾ NPC cells reveals enriched mitochondrial OxPhos proteins.
• •OxPhos proteins mediate NLRP3 inflammasome activation through mtROS.
• •OxPhos proteins, NDUFB8 and ATP5B are correlated with NPC local recurrence.