直接遗忘效应中认知抑制机制研究新进展

随着认知抑制研究的兴起,作为测量认知抑制能力的主要方法,直接遗忘效应得到了不断深入的研究。本文简要介绍了直接遗忘效应的研究范式,并就直接遗忘的内在机制是"选择性复述"的作用,还是"认知抑制"的作用展开讨论。在此基础上还就个体抑制能力的发展进程及其应用价值的研究进展做了简要介绍,并指出了已有研究存在的一些问题。     

Chemistry and selection

Life is the product of chemistry, which obeys deterministic laws, and of natural selection, which operates on variants offered to it by chance, but may, in a number of cases, have been provided with a sufficiently extensive array of variants to be optimizing. Thus, the origin and evolution of life have been largely shaped by the contingency of environmental conditions. The possibility remaining open for consideration is that certain critical conditions are sufficiently reproducible for life to arise and even to evolve into conscious, intelligent beings elsewhere in the universe.     

Expansion of the scaffold diversity for the development of highly selective butyrylcholinesterase (BChE) inhibitors: Discovery of new hits through the pharmacophore model generation,virtual screening and molecular dynamics simulation

Butyrylcholinesterase (BChE) is recently considered as a new target for the treatment of Alzheimer’s disease (AD). There is an increasing interest in the development of BChE inhibitors. In the present study, a set of pharmacophore models for BChE was developed and validated. Based on the models, virtual screening was performed on five compound collections, from which seventeen potential hits were retained for biological investigation. In total, eight of these seventeen potential hits showed selective BChE inhibitory activity. Moreover, four compounds displayed IC₅₀ values in sub-micromolar range on eqBChE and three displayed IC₅₀ values < 2 μM on huBChE. The diverse scaffolds of the active compounds provided good starting point further development of selective BChE inhibitors. As far as we concerned, here we disclose the first selective pharmacophore model targeting BChE. The high rate of the model in the identification of active hits indicates it is a valuable tool for the development of selective BChE inhibitors, which may benefit the treatment of AD.     

Identification of 10-dehydrooxyglycyuralin E as a selective human estrogen receptor alpha partial agonist

Selective estrogen receptor modulators (SERMs) act as either agonist or antagonist of estrogen receptor (ER) in a tissue selective manner and have been used in several diseases such as breast cancer, postmenopausal syndrome, osteoporosis, and cardiovascular diseases. However, current SERMs may also increase the risk of serious side effects and trigger drug resistance. Herein, a screening program, that was designed to search for novel SERMs, resulted in the identification of a series of 2-arylbenzofuran-containing compounds that are ligands for ERα, when applying the Gaussia-luciferase reporter assay. One of these compounds, 10-dehydrooxyglycyuralin E (T9) was chemically synthesized. T9 showed anti-estrogenic/proliferative activity in ERα-positive breast cancer cells. Pretreatment of T9 prevented the mRNA expression of GREB1, which is an estrogen response gene. Furthermore, by an in silico docking simulation study we demonstrated that T9 showed interactions directly to ERα. Taken together, these results demonstrated that T9 is a candidate of SERMs and a useful seed compound for the foundation of the selective activity of SERMs.     

Kinetics improvement of high-grade sulphides bioleaching by effects separation

Abstract: The kinetics of bioleaching of sulphide concentrates by Thiobacillus ferrooxidans can be improved by performing separately the two operations relating the two effects involved in the indirect contact mechanism, (1) chemical leaching and (2) biological oxidation of the Fe2+ produced in the chemical stage (IBES: Indirect Bioleaching with Effects Separation). This scheme permits the separate enhancement of each stage. On the one hand, the chemical attack of the ferric iron to sulphides can be performed at a higher temperature. On the other hand, the biological oxidation stage is more effective when biofilm models are applied. At the same time, inhibitory phenomena produced as a result of the bacterial breaking caused by the abrasion of the solid particles on microorganisms are prevented. In this work the 1BES process has been applied to a Spanish copper-zinc and a copper sulphide concentrate. The objective has been to selectively dissolve zinc, which may be recovered by solvent exraction, the remaining residue being a copper concentrate suitable for pyrometallurgical treatment. The attributes of moderate temperature, atmospheric pressure, low cost of the leaching agent, flexibility and effectiveness make the process very attractive from an economic point of view.     

Gradient enhanced selective experiments in the 1H NMR chemical shift assignment of the skeleton and side-chain resonances of stigmasterol, a phytosterol derivative

The applicability of homonuclear gradient enhanced NMR experiments is demonstrated in the structure determination of steroid derivatives using stigmasterol as a model compound. High resolution 1H NMR spectra of steroids very often display well resolved multiplets usually in the low-field region, and these signals can be used as starting points in several selective NMR experiments to study scalar (J coupling), and dipolar (NOE) interactions. Selective excitation was carried out using a double pulsed-field gradient spin-echo sequence (DPFGSE) in which 180 degrees Gaussian pulses are sandwiched between sine shaped z-gradients. Scalar interactions were studied by homonuclear DPFGSE-COSY, DPFGSE-relay-COSY and DPFGSE-TOCSY experiments, while DPFGSE-NOESY was used to monitor spatial environment of the selectively excited proton. These methods provided unambiguous assignments for signals of the main skeleton and the side-chain of the steroid molecule. In addition, they allowed determination of the conformationally important homonuclear proton-proton coupling constants (J).     

Allosteric interactions among pyrethroid,brevetoxin, and scorpion toxin receptors on insect sodium channels raise an alternative approach for insect control

Intensive pyrethroid use in insect control has led to resistance buildup among various pests. One alternative to battle this problem envisions the combined use of synergistically acting insecticidal compounds. Pyrethroids, scorpion - and β-toxins, and brevetoxins bind to distinct receptor sites on voltage-gated sodium channels (NaChs) and modify their function. The binding affinity of scorpion -toxins to locust, but not rat-brain NaChs, is allosterically increased by pyrethroids and by brevetoxin-1. Brevetoxin-1 also increases the binding of an excitatory β-toxin to insect NaChs. These results reveal differences between insect and mammalian NaChs and may be exploited in new strategies of insect control.     

Global Positioning System (GPS) location accuracy improvement due to selective availability removal

Global Positioning System (GPS) is an important new technology for spatio-temporal behaviour studies of animals. Differential correction improves location accuracy. Previously, it mostly removed partially the influence of Selective Availability (SA). SA was deactivated in May 2000. The aim of this study was to quantify the influence of SA cancellation on location accuracy of various GPS receivers. We tested the accuracy of locations obtained from non-differential and differential GPS animal collars before and after SA removal. We found a significant improvement in accuracy for both types of GPS collars. However, differential GPS still provides more accurate locations.     

The impact of restrictive entry criterion during the placebo lead-in period

In the study of depression, most randomized clinical trials have design features that attempt to sample from a stable patient population. One commonly used design feature is to require patients to maintain some minimum baseline symptom severity score during a placebo lead-in period. One intent of this design feature is to evaluate the behavior of patients prior to administration of active medication. If, during the lead-in period, patients do not maintain minimum symptom severity, the patients are excluded from the remainder of the study, the theory being that the excluded patients are not part of a stable patient population and hence are not likely to demonstrate efficacy of a truly effective treatment. This presentation investigates the effectiveness of a restrictive entry criterion and proposes an alternative explanation for what is usually defined as placebo response.     

A Theoretical Model for the Association Probabilities of Saturated Phospholipids from Two-Component Bilayer Lipid Membranes

The non-random mixing of biomembrane components, especially saturated phospholipids, exhibits important consequences in molecular biology. Particularly, the distribution of lipids within natural and model membranes is strongly determined by the selective association processes. These processes of phospholipids take place due to the cooperative modes in multiparticle systems as well as the specific lipid-lipid interactions both in the hydrophobic core and in the region of the polar headgroups. We demonstrated that the investigation of the selective association processes of saturated phospholipids might contribute to the insight of the lipid domains appearance inside the bilayer membranes. The association probabilities of like-pairs and cross-pairs from a binary mixture of saturated phospholipids were tested for both parallel and anti-parallel alignments of the polar headgroups. The present model confirms the experimental evidence for saturated phospholipids to have a high tendency for association in parallel configuration of the electric dipole moments of the polar headgroups whether the cross-sectional area of the polar headgroup is in an usual range of 25-55 2. There are three major lipid domains in a binary mixture of saturated phospholipids: (i) lipid domains in non-mixed phase of the first mixture component, in parallel alignment of the polar headgroups; (ii) lipid domains in non-mixed phase of the second mixture component, in anti-parallel alignment of the polar headgroups; (iii) lipid domains in mixed phase. We think that the selective association processes of phospholipids are neither exclusively, nor only involved in promoting the lipid domains appearance through bilayer phospholipid membranes.