Molecular mechanisms of allosteric probe dependence in μ opioid receptor

Allostery is one of the most important features of proteins. It greatly contributes to the complexity of life, since it enables possibility of precise tuning of protein function, as well as performing more than one function per protein. Probe dependence is one of the unique features of allostery. It allows a protein to respond differently to the same allosteric modulator when different drugs or transmitters are bound. Unfortunately, allosteric mechanisms are difficult to investigate experimentally. Instead, they can be reproduced artificially in simulations. We simulated in silico a native-like cell membrane fragment with an active-state human μ opioid receptor (MOR) in order to investigate diverse effects of a receptor’s positive allosteric modulator on various agonists. Particular emphasis on native-likeness of the environment was put. We managed to reproduce the experimentally observed effects, which allowed us to take deeper insight into their underlying mechanisms. We found an allosteric pathway in the receptor, leading from the ligand binding site to the intracellular, effector site. We observed that the modulator affected the pathway, inducing different resultant responses for full and partial agonists.     

鸟类鸣声与个体适合度关系的研究进展

鸣声蕴藏着丰富的生物学信息,是鸟类间信息交流最主要的方式之一.本文综述了鸟类鸣声行为与包括个体状态(体征、激素水平和健康状况)、社会等级及繁殖(性选择和成效)在内的个体适合度关系的研究进展.文章总结发现,鸟类的鸣声水平与单一体征参数关系的研究结果不稳定,鸣声可能受个体内部的多种激素调控,并与个体的社会等级有直接关系.雌...     

Experiments on Nitrogen and Phosphorus Release by Chironomus ex gr. plumosus from the Sediments of Lake Balaton,Hungary

Sediment-water systems of Lake Balaton mud and tap water were constructed in plexiglass tubes and boxes for evaluation of changes in the nitrogen and phosphorus contents of overlying water as influenced by chironomid density and light conditions. Nitrogen flux from sediment was greatly influenced by denitrification process. The amount of TN released by chironomids amounted to about half of the yearly nitrogen fixation rate in Lake Balaton. Omnivorous chironomids increased the phosphorus content of the overlying water. The rate of release was density dependent. TP release rates ranged between 1–17 mg m⁻² day ⁻¹ over a range of densities 500–20,000 larvae m⁻². It became evident that aerobic sediment cores can be an important nutrient source in lakes where chironomids inhabit them at densities above 1,000 larvae m⁻².     

Mutual mate choice by mountain pine beetles: size‐dependence but not size‐assortative mating

1. Mutual mate choice may be rare, occurring when both sexes invest heavily in reproduction, mating opportunities are abundant, and individuals differ in quality. 2. Mountain pine beetles, Dendroctonus ponderosae (Curculionidae: Scolytinae) appear to meet the conditions for mutual mate choice. We introduced males to females in breeding sites and observed the occurrence and speed of a male entering a female's gallery. We tested for consequences of mutual mate choice, namely condition‐dependent choosiness and assortative mating. 3. Males were more likely to enter a female's gallery when the gallery was in a smaller tree with less resin production and when the gallery was larger. Female body size and condition did not influence the probability of entry. Larger males were less likely to enter a gallery than were smaller males, probably because of size‐dependent choosiness rather than physical limitations. 4. Small males took longer to enter galleries of large females than of small females, whereas large males entered as quickly into galleries of large females as small females. This suggests size‐dependent choosiness by females. 5. No assortative mating by body size was detected, probably because males appeared to choose on the basis of female‐associated resources rather than on female traits.     

Interspecific competition in Drosophila II. Competitive outcome in some 2–resource environments

Populations of Drosophila metanogaster and D. simulans were made to compete in a number of 2– resource environments. The resources used were all based on a standard Drosophila medium and differed from each other only in their concentrations of ethanol. Each experiment comprised three cages started at a species–frequency of 0.8 D. melanogaster and three at 0.2 D. melanogaster. This enabled screening for a wide range of equilibria.
Reversal of competitive superiority was achieved (unintentionally) by raising the alcohol level of one of the resources. Thus while D. simulans won in an environment with media containing 0 and 896 ethanol, D. melanogaster won if the ethanol concentrations were 0 and 10%, or 0 and 12%. This parallels the reversal of dominance reported earlier for single–resource systems. However, in none of the 2–resource systems studied was there a stable equilibrium in species–frequency–in fact there was no significant frequency–dependence at all.
An artificial selection experiment produced a stock of D. melanogaster ovipositing a higher proportion of eggs on the alcoholic resource. Thus, this stock was more divergent from D. simulans , in at least one aspect of resource use, than was the original stock of D. melanogaster. However, competition between stock D. simulans and selected D. melanogaster showed no frequency–dependence. Again, reversal of competitive dominance was unintentionally achieved.
The implications of these results are discussed, and the need for a comprehensive study of resource–utilization in a pair of competing species is stressed.     

Presynaptic Dopaminergic Function in the Nucleus Accumbens Following Chronic Opiate Treatment and Precipitated Withdrawal

Naloxone treatment at three days following implantation of pellets containing morphine base increased uptake of tritiated dopamine by the nucleus accumbens but did not alter efflux of tritiated dopamine by the nucleus accumbens or tritiated norepinephrine by the hippocampus. At six days following placement of pellets containing morphine base, withdrawal score was increased after treatment with either saline or naloxone, indicating that animals were undergoing spontaneous opiate withdrawal. Fractional efflux of tritiated dopamine was decreased at this time point following intermittent stimulation with 317 and 1000 M 4-aminopyridine, for striatal slices obtained from animals pretreated with either saline or naloxone. For the nucleus accumbens at six days after placement of morphine pellets, similar decreases in the efflux of tritiated dopamine were only observed in slices obtained from naloxone treated animals. Fractional dopamine efflux was also diminished after in vitro exposure to rising concentrations of 4-aminopyridine, amphetamine, or cocaine for tissue obtained from the nucleus accumbens, but not for slices from the striatum at six days following morphine pellet implantation. In conclusion, deficits in dopamine efflux by the nucleus accumbens occur at a time when animals are undergoing spontaneous opiate withdrawal at six days following morphine pellet implantation, but do not occur at an earlier time point when withdrawal is precipitated by naloxone treatment. These deficits are apparent for brain slices obtained from the striatum or nucleus accumbens after exposure to rising concentrations of different in vitro treatments, with tissue obtained from the nucleus accumbens being more sensitive than the striatum to dopamine efflux produced by a wider range of treatments.     

电压门控Na^＋通道亚型及其功能——新的研究热点

依靠现代分子生物学技术及电生理的记录,探讨各种Ｎａ＾＋通道亚型在中枢与周边神经系统以及一些非兴奋性组织细胞中的分布,表达,突变及其对信息调控的功能特征,已成为当今神经生物学等学科发展中的一个研究新热点,本文将侧重对有关哺乳动物Ｎａ＾＋通道亚型的分类,在不同组织细胞中的分布及其表达调控的功能机制等一些研究进展做一简要的回眸。     

Rafts: scale-dependent, active lipid organization at the cell surface

Rafts have been conceptualized as lateral heterogeneities in the organization of cholesterol and sphingolipids, endowed with sorting and signaling functions. In this review we critically examine evidence for the main tenet of the 'raft hypothesis', namely lipid-dependent segregation of specific membrane components in the plasma membrane. We suggest that conventional approaches to studying raft organization wherein membranes are treated as passive, thermally equilibrated systems are unlikely to provide an adequate framework to understand the mechanisms of raft-organization in vivo. An emerging view of raft organization is that it is spatio-temporally regulated at different scales by the cell. This argues that rafts must be defined by simultaneous observation of components involved in particular functions. Recent evidence from the study of glycosylphosphatidyl inositol-anchored proteins, a common raft-marker, supports this picture in which larger scale, more stable rafts are induced from preexisting small-scale lipid-dependent structures actively maintained by cellular processes.     

Average protein density is a molecular-weight-dependent function

The mass density of proteins is a relevant basic biophysical quantity. It is also a useful input parameter, for example, for three-dimensional structure determination by protein crystallography and studies of protein oligomers in solution by analytic ultracentrifugation. We have performed a critical analysis of published, theoretical, and experimental investigations about this issue and concluded that the average density of proteins is not a constant as often assumed. For proteins with a molecular weight below 20 kDa, the average density exhibits a positive deviation that increases for decreasing molecular weight. A simple molecular-weight-depending function is proposed that provides a more accurate estimate of the average protein density.