Differential Transmitter Release from Nerve Terminals Isolated from Basal Ganglia and Substantia Nigra

Abstract: The K⁺-induced release of amino acids and dopamine from synaptosomes of basal ganglia and substantia nigra of sheep was studied. K⁺ (56 mM) caused an increase in the release of GABA from caudate, putamen, globus pallidus, and substantia nigra, the increased release being 227, 171, 198, and 366%, respectively, compared with samples incubated without stimulation. The release of glutamate was also increased by 56 mM-K⁺ (136–183%) from all regions except the globus pallidus, and a significant release of aspartate was only seen in response to K⁺ stimulation of synaptosomes from putamen (50%). Veratrine (75 μM) also stimulated a similar pattern of amino acid release from these regions. Regional correlation was shown between the presence of an uptake system for an amino acid and its evoked release. [¹⁴C]Dopamine formed from L-[U-¹⁴C]tyrosine was released only from caudate and putamen synaptosomes by K⁺ stimulation, the increases being 105% and 74%, respectively. Synthesis of [¹⁴C]dopamine from L-[U-¹⁴C]tyrosine occurred only in synaptosomes prepared from these two regions and was not detected in synaptosomes from substantia nigra or globus pallidus although whole-tissue homogenates of substantia nigra were able to synthesise dopamine.     

鼠李糖乳杆菌LV108及其发酵乳免疫调节作用的比较

目的探讨鼠李糖乳杆菌LV108及其发酵乳对免疫抑制小鼠免疫功能的调节作用。方法将BALB/c小鼠随机分为5组,每组10只,即空白组(正常小鼠)、模型组(免疫抑制小鼠)、药物组(免疫抑制小鼠食物中添加左旋咪唑)、LV108菌悬液组(免疫抑制小鼠食物中添加LV108菌悬液)和LV108发酵乳组(免疫抑制小鼠食物中添加LV108发酵乳),除空白组外其余组构建免疫抑制小鼠模型。干预4周后,分别测定各组小鼠体质量和脏器指数,血清中白细胞介素2(IL2)、肿瘤坏死因子α(TNFα)和免疫球蛋白G(IgG)含量,血清溶血素含量、耳肿胀度和肝、脾巨噬细胞吞噬能力。结果相比模型组,LV108菌悬液组和LV108发酵乳组小鼠体质量增长速度、脏器指数、血清IL2与IgG水平、血清溶血值、耳肿胀度和巨噬细胞吞噬能力显著升高(均P<0.05);在脾脏指数、血清IL2与TNFα水平、血清溶血素含量和耳肿胀度免疫指标上,LV108菌悬液组与LV108发酵乳组之间比较差异具有统计学意义(均P<0.05)。结论LV108菌体及发酵乳对免疫抑制小鼠具备较全面的免疫调节作用,均可提高小鼠的自身免疫力;LV108发酵乳对小鼠的免疫调节作用强于LV108菌体。     

Defining salivary biomarkers using mass spectrometry-based proteomics: a systematic review

Recent advancements in mass spectrometric proteomics provide a promising result in utilizing saliva to explore biomarkers for diagnostic purposes. However, the issues of specificity or redundancy of disease-associated salivary biomarkers have not been described. This systematic review was therefore aimed to define and summarize disease-related salivary biomarkers identified by mass spectrometry proteomics. Peer-reviewed articles published through July 2009 within three databases were reviewed. Out of 243 articles, 21 studies were selected in this systematic review with conditions including Sj?gren's syndrome, squamous cell carcinoma, dental caries, diabetes, breast cancer, periodontitis, gastric cancer, systemic sclerosis, oral lichen planus, bleeding oral cavity, and graft-versus-host disease. The sample size ranged from 3-41 in both diseased and control subjects, with no consensus on sample collection protocol. One hundred eighty biomarkers were identified in total; 87 upregulated, 63 downregulated, and 30 varying based on disease. Except for Sj?gren's syndrome, the majority of studies with the same disease produce inconsistent biomarkers. Larger sample size and standardization of sample collection/treatment protocol may improve future studies.     

Isolation of Fidelity Variants of RNA Viruses and Characterization of Virus Mutation Frequency

RNA viruses use RNA dependent RNA polymerases to replicate their genomes. The intrinsically high error rate of these enzymes is a large contributor to the generation of extreme population diversity that facilitates virus adaptation and evolution. Increasing evidence shows that the intrinsic error rates, and the resulting mutation frequencies, of RNA viruses can be modulated by subtle amino acid changes to the viral polymerase. Although biochemical assays exist for some viral RNA polymerases that permit quantitative measure of incorporation fidelity, here we describe a simple method of measuring mutation frequencies of RNA viruses that has proven to be as accurate as biochemical approaches in identifying fidelity altering mutations. The approach uses conventional virological and sequencing techniques that can be performed in most biology laboratories. Based on our experience with a number of different viruses, we have identified the key steps that must be optimized to increase the likelihood of isolating fidelity variants and generating data of statistical significance. The isolation and characterization of fidelity altering mutations can provide new insights into polymerase structure and function^1-3. Furthermore, these fidelity variants can be useful tools in characterizing mechanisms of virus adaptation and evolution^4-7.     

中国环境管理分区:方法与方案

我国生态环境可持续性及其影响因素的区域差异显著,各地区环境管理面临的主要挑战和需要优先解决的生态环境问题不同。进行环境管理分区,根据各地区生态环境特征及其影响因素的差异性,制定有针对性的环境管理政策,将有效促进我国区域生态环境的整体优化。采取定性和定量分析相结合的方法进行我国环境管理分区。首先,在我国3大自然区的基础上,根据我国的自然地理格局和已有的相关区划成果,把我国划分为4个环境管理大区,包括:南部季风区、北部季风区、西北干旱区和青藏高寒区。其次,通过建立的包含13个指标的环境管理分区指标体系,采用一维化欧式距离法分析各环境管理大区下相邻省级行政区环境特征的相似性,把环境特征相似性大的相邻地区划分到同一分区,得到以省级行政区为基本单元的我国环境管理分区方案。然后,结合地区间历史渊源和区域未来发展趋势分析,对基于相似性分析的初步分区方案进行调整,把我国划分为8个以省级行政区为基本单元环境管理区。最后,根据相关调整原则和方法,对以省级行政区为基本单元的分区方案的边界线进行调整,得到以地级行政区为基本单元的分区方案,把我国划分为东北地区、华北平原区、华北山地与高原区、东南沿海地区、长江流域中游地区、西南地区、西北干旱区和青藏高寒区8个环境管理区。     

Can climate matching predict the current and future climatic suitability of the UK for the establishment of non-native birds?

Capsule: Current UK distributions of non-native birds poorly match areas identified as being climatically suitable.

Aims: Non-native species are spreading at unprecedented rates and though invasions are expected to increase under climate change, evidence for this is mixed. We assess climatic suitability throughout the UK based on the apparent match to the climate in species’ native ranges and investigate potential climatic limitation within the non-native range.

Methods: Climate was characterized within polygons representing the native ranges of 167 potentially invasive species. Parts of the UK with current and future climate similar to that in the native range were deemed climatically suitable. The incidence of recent observations inside and outside suitable areas was used to test hypotheses about climatic limitation of non-native ranges.

Results: Climate matching suggests that 69 of 167 non-native bird species could currently find climatically suitable areas for establishment in the UK. Future climate change would see this number increase by 14% by 2080. However, observed occurrences of non-native species in the UK were not significantly correlated to climatic suitability. Only 44 of the 69 species with suitable climate in the UK were present. Moreover, 85% of species observed in the UK had some UK occurrences in climatically unsuitable areas and for 57 species their entire UK range was in climatically unsuitable areas. Similar results were apparent for the subset of 12 species with established UK populations.

Conclusions: Climate matching provides a relatively poor indication of the extent of current and future suitable areas because species can adapt to new climates or other factors constrain the native range and many climatically suitable areas are currently unoccupied. Improvements to climate matching techniques and ongoing surveillance are required to refine predictions to support effective management policies.     

Initial Fitness Recovery of HIV-1 Is Associated with Quasispecies Heterogeneity and Can Occur without Modifications in the Consensus Sequence

Background

Fitness recovery of HIV-1 “in vitro” was studied using viral clones that had their fitness decreased as a result of plaque-to-plaque passages.

Principal Findings

After ten large population passages, the viral populations showed an average increase of fitness, although with wide variations among clones. While 5 clones showed significant fitness increases, 3 clones showed increases that were only marginally significant (p<0.1), and 4 clones did not show any change. Fitness recovery was not accompanied by an increase in p24 production, but was associated with an increase in viral titer. Few mutations (an average of 2 mutations per genome) were detected in the consensus nucleotide sequence of the entire genome in all viral populations. Five of the populations did not fix any mutation, and three of them displayed marginally significant fitness increases, illustrating that fitness recovery can occur without detectable alterations of the consensus genomic sequence. The investigation of other possible viral factors associated with the initial steps of fitness recovery, showed that viral quasispecies heterogeneity increased between the initial clones and the passaged populations. A direct statistical correlation between viral heterogeneity and viral fitness was obtained.

Conclusions

Thus, the initial fitness recovery of debilitated HIV-1 clones was mediated by an increase in quasispecies heterogeneity. This observation, together with the invariance of the consensus sequence despite fitness increases demonstrates the relevance of quasispecies heterogeneity in the evolution of HIV-1 in cell culture.